Benign prostatic hyperplasia(BPH) in Herbs Points of View

 Kyle J. Norton(Draft Article)

Benign prostatic hyperplasia(BPH) is defined as a condition of increased in the number of cells of prostate gland, causing partial, or sometimes virtually complete obstruction of the urinary tract. According to statistic, BPH commonly starts at age of 30 and symptoms usually can not be realized until age of 50. More than half of men between age of 60-70 are experience symptoms of BPH and only 10% are required treatment. Epidemiological studies, linking herbal medicine in reduced risk of benign prostate hyperplasia have produced a certain positive result, but multi centers and large sample size are necessary to identify the principle ingredient to validate these result.

1. Serenoa repens (Saw palmetto)
Saw Palmetto, is a small palm like tree of the genus in the genus Serenoa, belonging to the family, native to o southeastern North America. The herb has been used in The North American Seminole Indians for infertility, PMS, reproductive or urinary tract problems, urinary tract infections, stomach aches, indigestion and dysentery, etc. In rat study, a liposterolic extract of saw palmetto  showed to inhibited the contractions of prostate gland consistently with smooth muscle relaxant activity(1). In a total of total of 297 patients recruited, with 87 into the group TAM, 97 into the group SR and 81 into the group tamsulosin (TAM) + Serenoa repens (SR), SR and TAM treatment of BPH had showed to be efficacy as in alone, a combined therapy (TAM + SR) does not provide extra benefits(2). On the mRNA gene expression profiles of two representative models of BPH,  BPH1 cell line and primary stromal cells derived from BPH, lipidosterolic extract of Serenoa repens (LSESr) significantly altered gene expression patterns, categorized as part of proliferative, apoptotic, and inflammatory pathways(3). Unfortunately, a meta-analysis of two high quality long-term trials (n = 582), conducted by the,  showed no effect of Sere noa repens, at double and triple doses, in improving urinary flow measures or prostate size in men with lower urinary tract symptoms consistent with BPH(4).

2. Cuban royal palm
Cuban royal palm is a genus Roystonea, belonging to the family  Arecoideae, native to southern Florida, Mexico and parts of Central America and the northern
Caribbean. The roots of the tree has been used as a diuretic, and for treatment of diabetes. In rat study, 
D-004, a lipid extract from Cuban royal palm fruits incomparison of Saw palmetto and tamsulosin, a 
selective alpha(1A)-adrenoceptor antagonist, indicated that D-004 was moderately more effective
 than Saw palmetto, a phytotherapeutic standard
used to treat BPH, but less effective than tamsulosin, a selective alpha(1A)-adrenoceptor antagonist(5).
Other study of the same by the Center of Natural Products from the National Center for Scientific
Research, showed that oral administration of D-004 administered orally for 14 days prevented the
increase of prostate size and the testosterone-induced prostate enlargement with in rodents(6)(7).

3. Prunus africana
Prunus africana. also known as Red Stinkwood, is a an evergreen tree,  genus Prunus, belonging to the family Rosaceae, native to the montane regions of Sub-Saharan Africa. The herb has been used in traditional medicine to treat fevers, malaria, wound dressing, arrow poison, stomach pain, purgative, kidney disease, appetite stimulant, gonorrhoea, and insanity(8).
Pygeum africanum extract, in a multicentre trial in central Europe, treatment found to be effective in changes in subjective scores, International Prostate Symptom Score (IPSS) and QoL after the two-month period were highly statistically significant with mean improvements of 40% and 31% and with the overall result of a substantial improvement in QoL(9)(10). Although many evidence suggests that P. africanum modestly and significantly, improved urologic symptoms and flow measures, further research is needed using standardized preparations of P. africanum to determine its long-term effectiveness and ability to prevent complications associated with benign prostatic hyperplasia(11).

4. Green tea 
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. The levels or activity of androgen hormones are associated to the risk of BPH, green tea catechin, (-)epigallocatechin-3-gallate, exhibited its modulation of androgenic activity that may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia(12). 5 alpha-reductase activity may be involved in the development of benign prostatic hyperplasia. The Ben May Institute for Cancer Research, and The Tang Center for Herbal Medicine Research study showed green tea catechin (-)-epigallocatechin gallate (EGCG) is potent inhibition in cell-free and in replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors(13). the study by the Oregon State University, also showed that in the study of male n, noble rats implanted with estradiol and testosterone were divided into 4 dietary groups: control, soy, tea, or soy+tea, the combinartion of  soy and tea attenuated prostate malignancy by decreasing prostate hyperplasia(14). Also, green tea catechin, (-)epigallocatechin-3-gallate, According to Dr. Liao S., may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia, due to its modulation of androgenic activity, possibly through increasing in testosterone metabolism, down-regulation of androgen receptors or activation of oestrogen receptors (15).

5. Licorice
Licorice (Glycyrrhiza Glabra) also known as sweetwood, is the genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc. Glycyrrhiza glabra extract with doses of 150 and 300 mg/kg showed a significant reduction in prostate weight, total estosterone and VP epithelium/stroma ratio (V/V)(16).

6. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. A multicenter case-control study of 1369 patients with BPH and 1451 controls, indicated an inverse association of intake of garlic related to the risk of BPH, consistent across age strata(17). Other researchers suggested that garlic potential in treating BPH due to its anti-inflammatory, anti-cancer and antioxidant effects as well as its effectiveness for the treatment of prostate cancer and relief of BPH symptoms(18).

7. Epilobium parviflorum
Epilobium parviflorum also known as Smallflower Hairy Willowherb, is a genus Epilobium, belonging to the family Onagraceae. The herb has been used in traditional medicine as an antioxidant and 
antiinflammatory agent and  in treating BPH, bladder and kidney, etc.
According to the study by Farmakognózia Intézet, willow-herb possess remarkable antioxidant and COX-inhibitory action and may be effective in treating benign prostatic hyperplasia (BPH)(19). Other study suggested a protective effect against benign prostatic hyperplasia (BPH), through inhibited oxidative damage, generated in fibroblast cells, decreased the PGE(2) release and inhibited COX-enzyme(20).

8. Urtica dioica
Sting Nettle is a flower plant in the genus Urtica, belonging tothe family Urticaceae, native to Europe, Africa, Asia, and North America.The herb has been used in traditional medicine as diuretic and laxative agent and to treat diarrhea and urinary disorders, to relieve pain, treat arthritis, asthma, bronchitis, sinusitis, etc.
In a 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial with placebo in 620 patients conducted by Shaheed Beheshti University of Medical Sciences, Urtica dioica showed to improve International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR) and prostate size(21). Composition of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) found to improve  the amelioration of LUTS as measured by the I-PSS, obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms of BPH(22)(23). Bazoton uno (459 mg dry extract of stinging nettle roots), in a study of a total of 246 patients, reduced irritative symptoms and BPS-associated complications due to the postulated antiphlogistic and antiproliferative effects(24).

9. Ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root). Ginseng, one of the most popular herb has been used in human history in treating vary types of diseases. Panax ginseng or Red ginseng water extract and its chemical constituent 20(S)-Rg3 showed to inhibit testosterone-induced cell proliferation, arrested cell cycle by inducing p21 and p27, and induced apoptosis, through inhibition of testosterone-induced expression of human kallikrein-3 mRNA and activation of androgen receptor (AR)(25).

10. Rye (Secale cereal)
Rye (Secale cereal) is a grass in the genus Secale, belonging to the family Poaceae, native to the  central and eastern Turkey, and in adjacent areas. The herb has been used
in folk medicine seed as laxative due to its fibrous seed coat. Cernilton, isolated
from the rye-grass pollen Secale cereal, in randomized controlled trials or controlled clinical trials
comparing Cernilton with placebo or other BPH medications in men with BPH showed a modestly
improves overall urologic symptoms including nocturia(26). In a 444 men enrolled in 2
placebo-controlled and 2 comparative trials lasting from 12 to 24 weeks, conducted by Department
of Veterans Affairs Coordinating Center,  Cernilton improved "self rated urinary symptoms", reduced
nocturia, but not improve urinary flow rates, residual volume or prostate size compared to placebo or
the comparative study agents(27). 

Taking altogether, without going into reviews, herbal medicine mentioned above may be effective in
reduced risk of Benign prostatic hyperplasia(BPH), but further studies are necessary to identify the
principle ingredients through comparison with Western medicine in use with large sample size and
multi centers involvement. As always, All articles written by Kyle J. Norton are for information &
education only, please consult your Doctor & Related field specialist before applying
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References
(1) Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): Effects on rat prostate contractility by Chua T¹, Eise NT², Simpson JS³, Ventura S(PubMed)
(2) Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia? byArgirović A¹, Argirović D².(PubMed)
(3) Lipidosterolic extract of serenoa repens modulates the expression of inflammation related-genes in benign prostatic hyperplasia epithelial and stromal cells by Sirab N¹, Robert G, Fasolo V, Descazeaud A, Vacherot F, Taille Ade L, Terry S.(PubMed)
(4) Serenoa repens for benign prostatic hyperplasia by Tacklind J¹, Macdonald R, Rutks I, Stanke JU, Wilt TJ.(*PubMed)
(5) Effect of D-004, a lipid extract from the Cuban royal palm fruit, on atypical prostate hyperplasia induced by phenylephrine in rats by Arruzazabala ML¹, Más R, Molina V, Noa M, Carbajal D, Mendoza N.(PubMed)
(6) Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats by Noa M¹, Arruzazabala ML, Carbajal D, Más R, Molina V.(PubMed)
(7) Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents by Arruzazabala ML¹, Carbajal D, Más R, Molina V, Rodríguez E, González V.(PubMed)
(8) Stewart KM."The African cherry (Prunus africana): can lessons be learned from an over-exploited medicinal tree?." [Review] Journal of Ethnopharmacology. 89(1):3-13, 2003 Nov.
(9)Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe by Breza J¹, Dzurny O, Borowka A, Hanus T, Petrik R, Blane G, Chadha-Boreham H.(PubMed)
(10) Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension by Chatelain C¹, Autet W, Brackman F.(PubMed)
(11) Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis by Ishani A¹, MacDonald R, Nelson D, Rutks I, Wilt TJ.(PubMed)
(12) The medicinal action of androgens and green tea epigallocatechin gallate by Liao S.(PubMed)
(13) Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols by Hiipakka RA¹, Zhang HZ, Dai W, Dai Q, Liao S.(PubMed)
(14) Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFκB pathway in the Noble rat model by Hsu A¹, Bruno RS, Löhr CV, Taylor AW, Dashwood RH, Bray TM, Ho E.(PubMed)
(15) The medicinal action of androgens and green tea epigallocatechin gallate by Liao S.(PubMed)
(16) Antiandrogenic activities of Glycyrrhiza glabra in male rats by Zamansoltani F¹, Nassiri-Asl M, Sarookhani MR, Jahani-Hashemi H, Zangivand AA.(PubMed)
(17) Onion and garlic intake and the odds of benign prostatic hyperplasia by Galeone C¹, Pelucchi C, Talamini R, Negri E, Dal Maso L, Montella M, Ramazzotti V, Franceschi S, La Vecchia C.(PubMed)
(18) Is garlic a promising food for benign prostatic hyperplasia and prostate cancer? by Devrim E¹, Durak I.(PubMed)
(19) [Epilobium parviflorum--in vitro study of biological action].[Article in Hungarian] by Hevesi Tóth B¹, Kéry A.(PubMed)
(20) Antioxidant and antiinflammatory effect of Epilobium parviflorum Schreb by Hevesi BT¹, Houghton PJ, Habtemariam S, Kéry A.(PubMed)
(21) Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study by Safarinejad MR.(PubMed)
(22) Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial by Lopatkin N¹, Sivkov A, Walther C, Schläfke S, Medvedev A, Avdeichuk J, Golubev G, Melnik K, Elenberger N, Engelmann U.(PubMed)
(23) Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms--long-term follow-up of a placebo-controlled, double-blind, multicenter trial by Lopatkin N¹, Sivkov A, Schläfke S, Funk P, Medvedev A, Engelmann U.(PubMed)
(24) [Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS). Results of a randomized, double-blind, placebo controlled multicenter study after 12 months].

[Article in German] by Schneider T¹, Rübben H.(PubMed)
(25) Red ginseng and 20(S)-Rg3 control testosterone-induced prostate hyperplasia by deregulating androgen receptor signaling by Bae JS¹, Park HS, Park JW, Li SH, Chun YS.(PubMed)
(26) Cernilton for benign prostatic hyperplasia by Wilt T¹, Mac Donald R, Ishani A, Rutks I, Stark G.(PubMed)
(27) systematic review of Cernilton for the treatment of benign prostatic hyperplasia by MacDonald R¹, Ishani A, Rutks I, Wilt TJ.(PubMed)

 

Ovarian Cancer in B12 Points of View

  Kyle J. Norton(Draft Article)

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some vitamins have showed to inhibit the progression of cancer with little or no side effects.

Vitamin B12, also known as cobalamin, a water-soluble vitamin, found abundantly in a variety of foods, such as fish, shellfish, meat, eggs, dairy products, etc. plays an important role in regulating the functions of nervous system and formation of blood.

Epidemiological studies, linking vitamin B12 in reduced risk of ovarian cancer have drawn into inconclusive results. Suggestion of Folate, methionine, vitamin B(6) and vitamin B(12) may influence carcinogenesis due to their roles in the one-carbon metabolism pathway. In a study among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008, have indicated that One-carbon metabolism(metabolic network of interdependent biosynthetic pathways) related nutrients,  may lower ovarian cancer risk(1). Nitrosylcobalamin (NO-Cbl), a chemotherapeutic pro-drug derived from vitamin B12 has been found effectively in antiproliferative activity against several human cancer cell lines, including ovarian carcinoma (NIH-OVCAR-3) cells, through induction of apoptosis via a death receptor/caspase-8 pathway(2). In patients with epithelial ovarian cancer under treatment of Paclitaxel (T) and Carboplatin (J) combination chemotherapy, vitamin B12 was effective in relieving symptoms of arthralgia and muscular pain(3).

Taking altogether, vitamin B12 may be effective in reduced riak and treatment of ovarian cancer, but large sample and multu centers studies to validate its effects are necessary. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying. Over doses of the vitamin may induce symptoms of toxicity, including headache, giddiness and abnormal heart functioning, etc., please make sure to follow the guideline of the Institute of Medicine of the National Academies.
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References
(1) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR¹, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)
(2) Nitrosylcobalamin promotes cell death via S nitrosylation of Apo2L/TRAIL receptor DR4 by Tang Z¹, Bauer JA, Morrison B, Lindner DJ.(PubMed)
(3) [The efficacy of Shakuyaku-Kanzo-to for peripheral nerve dysfunction in paclitaxel combination chemotherapy for epithelial ovarian carcinoma].

[Article in Japanese by Fujii K¹, Okamoto S, Saitoh K, Sasaki N, Takano M, Tanaka S, Kudoh K, Kita T, Tode T, Kikuchi Y.(PubMed)

Ovarian Cancer in Folate Points of View

 Kyle J. Norton(Draft Article)

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.
Folate, also known as folic acid, vitamin B9, is a water soluble vitamin, found abundantly in leafy vegetables, citrus fruits, beans, whole grain, etc. The vitamin plays an important role in synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in certain biological reactions, production of red blood cells for anemia prevention.

Epidemiological studies, focusing folate in reduced risk of ovarian cancer have been inconclusive.
Folate, a member of B vitamin plays an important role in DNA synthesis and methylation, may process an anti proliferative effect in ovarain cancer cell lines. In the Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires, showed a little evidence to support the effect of folate in reduced risk of ovarian cancer(1) and  ovarian cancer survival(2). Other researchers suggested that no specific dietary factors are consistently associated with ovarian cancer risk, including folate(3), neither folate intake, MTHFR C677T polymorphism(4) nor one-carbon metabolism(5)
In a  prospective case-control study of the effect of Folic acid and methylenetetrahydrofolate reductase (MTHFR) against ovarian cancers in 215 ovarian cancer patients and 218 controls (all Chinese) between Jan. 2004 and Jan. 2007, indicated a result of a 2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a decreased risk of ovarian cancer in individuals with high folate intake(6). Intravenous administration of composition of  FA-NP showed more potent in anti proliferation than NP against both SKOV3 cells and SKOV3/TAX cells, but at the same dose failed to induce apoptosis and inhibit tumor nodule number. Of this result, the combined use of both FN-NP locally and targetly might prolong the survival time in patients with drug-resistant ovarian cancer(6). The Brigham and Women's Hospital study also supported the evidence of one-carbon metabolism related nutrients, especially vitamin B(7) and methionine, may lower ovarian cancer risk, among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008(8).

Taking all together, there are either enough evidences supported or unsupported  the effectiveness of folate in reduced risk of ovarian cancer. Further studies with large sample size and mutli centers studies are necessary to clarify the effect of folate in ovarian cancer risk. At the mean time as always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying

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References
(1) Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer by Webb PM¹, Ibiebele TI, Hughes MC, Beesley J, van der Pols JC, Chen X, Nagle CM, Bain CJ, Chenevix-Trench G; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group.(PubMed)
(2) Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival by Dixon SC¹, Ibiebele TI², Protani MM¹, Beesley J², Defazio A³, Crandon AJ⁴, Gard GB⁵, Rome RM⁶, Webb PM¹, Nagle CM⁷; on behalf of the Australian Ovarian Cancer Study Group.(PubMed)
(3) Dietary intake and ovarian cancer risk: a systematic review, by Crane TE¹, Khulpateea BR, Alberts DS, Basen-Engquist K, Thomson CA.(PubMed)
(4) Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer risk: evidence from the meta-analysis by Li C¹, Chen P, Hu P, Li M, Li X, Guo H, Li J, Chu R, Zhang W, Wang H.(PubMed)
(5) Relationship between dietary and supplemental intake of folate, methionine, vitamin B6 and folate receptor alpha expression in ovarian tumors by Kotsopoulos J¹, Hecht JL, Marotti JD, Kelemen LE, Tworoger SS(PubMed)
(6) Folate intake and methylenetetrahydrofolate reductase gene polymorphisms as predictive and prognostic biomarkers for ovarian cancer risk by Zhang L¹, Liu W, Hao Q, Bao L, Wang K.(PubMed)
(7) Folic acid-coupled nano-paclitaxel liposome reverses drug resistance in SKOV3/TAX ovarian cancer cells by Tong L¹, Chen W, Wu J, Li H.(PubMed)
(8) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR¹, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)

Skin aging in Herbs point of view

What cause aging? The question that has been asked throughout the human history, but it doesn't seem to get any answer but raises many more unanswered questions. While many theories try to answer the question by related aging to tear and wear of the body, others deal with how the organs and systems in the body develop and deteriorate overtime, etc.

Skin aging is one of most visible ageing process which occurs constantly in our skin organ. According to the Clinical Centre of Nis, certain plant extracts may have the ability to scavenge free radicals, to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin,  affect skin elasticity and tightness(a). Other suggested that free radicals induced domino effects in production of reactive oxygen species, can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system, leading  injuries damage regulation pathways of skin,  including wrinkles, roughness, appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks(b).
The degradation of the epidermal and dermal layers of the extracellular matrix (ECM), the non-cellular component present within all tissues and organs, such as UV Exposure, decline of lysosomal/endosomal cathepsin K, S and V activity(c) as well as some environmental factors on skin produces visible signs such as irregular dryness, dark/light pigmentation, sallowness, severe atrophy, telangiectases, premalignant lesions, laxity, leathery appearance and deep wrinkling, etc.,  cause modification of the surface of skin and the physical properties of that lead to skin aging.
Certain chemical ingredients, such as aloin, ginsenoside, curcumin, epicatechin, asiaticoside, ziyuglycoside I, magnolol, gallic acid, hydroxychavicol, hydroxycinnamic acids, hydroxybenzoic acids, etc.  derived from herbs have been found to be intergraded  into some cosmetic products in treating premature aging(d)

1. Aloe vera
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
In a study of a total of 30 healthy female subjects over the age of 45 recruited and received 2 different doses (low-dose: 1,200 mg/d, high-dose: 3,600 mg/d) of aloe vera gel supplementation for 90 days, aloe gel significantly improved wrinkles and elasticity in photoaged human skin, with an increase in collagen production in the photoprotected skin and a decrease in the collagen-degrading MMP-1 gene expression(1). In skin condition in the elderly caused by several incurable, but treatable, chronic diseases, researchers suggested that the use of lanolin, aloe vera, and parabens may contribute to  delayed hypersensitivity reaction and aging process(2). In photo aging, combination of sodium selenite and aloin in a certain range of concentration have shown protective effects against ultraviolet radiation induced fibroblast proliferation inhibition, oxidative injury, and decreased collagen synthesis(3).

2. Green tea
Green tea containing  more amount of antioxidants than any drinks or food with the same volume, is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Oxidative damage by reactive oxygen species (ROS) plays a major role in skin aging. Green tea extracted showed to inhibit the toxic ROS-induced skin death, through protection from H(2)O(2)-induced necrosis in a dose-dependent manner(4)(4a), improvement of the anti-wrinkle effects, through its antioxidant activity(5),  skin roughness, through moisturizing effects and enhancement of skin microrelief(6) and inhibition of skin inflammation for managing allergic contact dermatitis without skin toxicity(7). Combination of topical application of green tea and lotus, exhibited an anti aging effect on skin roughness (SEr), scaliness (SEsc), smoothness (SEsm), and wrinkling (SEw)(8) and  composition of a formulation containing 20 % green tea extract and 5 % rose oil, exhibited a skin barrier function for maintaining skin hydration, and protecting against anti-aging process(9).

3. Ginseng

Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root). In vivo Korean red ginseng showed to enhance extension of lifespan, increase resistance to most forms of disease, through regulation of organisms' metabolism(10), and reduce wrinkle formation through

inhibition of collagen degradation rather than increased collagen synthesis(11), protect against skin photodamage, through increasing the production of profilaggrin and filaggrin(12). Ginsenoside Rd, a chemical constituent of Ginseng also exerted its anti-oxidative effects through activation of  anti-oxidant enzymes and anti-inflammatory effects through down-regulation of NF-κB and the consequent expressional suppressions of iNOS and COX-2(13). On gene expression at the level of mRNAs and proteins in human skin cells, extracted from the roots of the Chinese herb Sanchi (Panax notoginseng, showed a significant positive effects against facial wrinkles and other symptoms of facial skin aging(14). In the study of red ginseng (RG) and fermented red ginseng (FRG) effects on aging skin, researchers at the Department of Food and Nutrition, Korea University found that FRG offers increased anti-wrinkle efficacy, whitening efficacy, and reduced toxicological potency compared to RG(15).

4. Turmeric

Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.

Curcumin, a major chemical compound found in turmeric, showed to have a protective effect against photo-damage on aging process(16). Antioxidantly, curcumin scavenged free radicals from skin cells, prevented trans-epidermal water loss, included a sun protection factor (SPF) of 15 or higher contribute to protect skin from wrinkles, leading to glowing and healthy younger skin(17) and induced cellular stress responses in normal human skin fibroblasts through phosphatidylinositol 3-kinase/Akt pathway and redox signaling(18).

5. Gotu Kola (Centella asiatica)

Gotu Kola also known as centella, is a annual plant of the genus, belonging to the family Mackinlayaceae, native to India, Sri Lanka, northern Australia, Indonesia, Iran, Malaysia, Melanesia, Papua New Guinea. The herb has been used in traditional medicine to treatnervous disorders, epilepsy, senility, premature aging, etc.

Asiatic acid, madecassic acid, asiaticoside and madecassoside, found in the titrated extract of Centella asiatica (TECA), showed to inhibit UVB-mediated damage in NHDFs through changes in the expression of specific miRNAs(19)(20). Preparation including asiaticoside found in Guto kota extract in a treatment of temporal periorbital wrinkles tested on 27 female volunteers by applied the cream twice a day to the region of interest for 12 weeks, showed a significant improvement of the periorbital wrinkles in majority of the volunteers(21). lipstick containing  asiaticoside also found to improve lip-wrinkle in in a double-blind placebo-controlled fashion of a total of 50 women(22). According to ¹LVMH Recherché, asiaticoside also stimulated collagen secretion which is the major components of skin dermis(23).

6. Sanguisorba officinalis

Sanguisorba officinalis is a genus Sanguisorba, belonging to the family Rosaceae, native to throughout the cooler regions of the Northern Hemisphere. The herb has been used in folk medicine to stop bloody dysentery, nosebleeds, and topically to treat burns and insect bites.

Ziyuglycoside I isolated from a Sanguisorba officinalis root extract reduced skin aging through increased the expression of type I collagen in a dose-dependent manner(24). In chronic Ultraviolet-B (UVB) irradiation causes of skin aging, the extract of Sanguisorba officinalis L. inhibited wrinkle formation, maintained skin elasticity, and inhibited the decrease of dermal elastic fiber linearity in the rat hind limb skin in a dose-dependent manner(25). 

7. Magnolia ovovata

Magnolia ovovata also known as Japanese Bigleaf Magnolia is the genus of Ovovata, belonging to the family Magnoliaceae, native to Japan. The herb has been used in traditional Chinese medicine
to treat various digestive problems, relieve stress, promote neuro-health, etc. According to

Nagoya City University Graduate School of Medical Sciences , Magnolia ovovata extract inhibited
NF-kappaB mediated gene expression, thus preventing skin photoaging processes through
keratinocyte hyperproliferation and degradation of collagen fibers in mice skin(26)(27).

8. Rhus verniciflua (Toxicodendron vernicifluum)
Rhus verniciflua is a genus Toxicodendron, belonging to the family Anacardiaceae, native to China
and the Indian subcontinent. The herb has been used in traditional Chinese medicine to treat internal
parasites and stop bleeding.

Rhus verniciflua Stokes (RVS), a most common used herbal plant in herbal medicine with various
biological properties was found to be effective in free radical scavengers due to contained flavonoid
derivatives, including fustin, quercetin, butein, and sulfuretin(29) which may protect the skin from
ROS aging. The ioactive phenolics in detoxified Rhus verniciflua Stokes (DRVS), including Gallic
acid showed to protect skin from aging through its antioxidative properties and by down-regulating
MMP-1 expression(28) and inhibited the degradation of extracellular matrix (ECM)(30).

9. Chamomile
Chamomile is also known as camomile, common name of many species daisy-like plants in the family
Asteraceae. The herb has been used in traditional medicine as antispasmodic and anti-inflammatory
constituents and to treat menstrual cramps and sleep disorders, reduce cramping and spastic pain in
the bowels, relieve excessive gas and bloating in the intestine, etc.
Chemical compounds bisabolol, silymarin, and ectoin found in chamomile and milk thistle may consist
the property to modulate the hydrogen peroxide (H2O2)-induced upregulation of ROS free radicals in
normal human skin fibroblasts(31). According to University of Copenhagen, oral administartion of
composition extact including chamomile improved skin lession of forehead, periocular and perioral
wrinkles, mottled pigmentation, laxity, sagging, under eye dark circles and overall apperance(32).

10. Cinnamon
Cinnamon is a spice derived from the inner bark of tree, native to South East Asia, of over 300 species
of the genus Cinnamomum, belonging to the family Lauraceae.. The herb has been use in herbal and
traditional medicine as anti-fungal and bacteria level to improve reproductive organ, prevent flatulence
and intestinal cramping, treat indigestion, diarrhea, bad breath, headache, migraine, etc.
According to Osaka Prefecture University, Cinnamon inhibited the breakdown of collagenous networks with aging results in hypoactive changes in the skin, through up-regulated both mRNA and protein expression levels of type I collagen without cytotoxicity. Cinnamaldehyde, a major active component, significantly increased the phosphorylation levels of the insulin-like growth factor-I (IGF-I) and its downstream signaling molecules such as insulin receptor substrate-1 and Erk1/2 in an IGF-I-independent manner(33).

 11. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, and from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
The study in the comparison of ginkgo (Ginkgo biloba), a mixture of tea and rooibos (Camellia sinensis and Aspalathus linearis) and soybean (Glycine soja) for their effects in potentiation in reduced skin wrinkle, showed that ginkgo biloba, is most effective in increased skin moisturization (27.88%) and smoothness (4.32%) and reduced roughness (0.4%) and wrinkles (4.63%)(34).


12. Rosemary Rosemary is a perennial herb with fragrant, evergreen, needle-like leaves, the genus Rosmarinus,
belonging to the family Lamiaceae. Its fresh and dried leaves has been used frequently in traditional
Mediterranean cuisine and as flavor foods while barbecuing. Rosnary has been used in traditional
medicine as an antiseptic, antioxidant, and antispasmodic agent to treat circulatory problem, eczema,
rheumatism, muscle pain, etc.
Rosemary containing flavonoid compounds with phenolic structures may potentiate in reduced reactive
oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects to
prevent skin damage(35). According to University of Catania, natural extract isolated from rosemary
leaves, showed to be effective in antiaging skin management due to its endogenous antioxidant
potential(36).

14. Grape seed extract
Grape Seed Extract is the commercial extracts from whole grape seeds that contains many
concentrations, including vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs),
etc..The herb has been used in traditional medicine as antioxidant, anti-inflammatory agents and to treat
 skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood
 vessels, lower cholesterol, etc.
Grape seed extract may be beneficial in promoting youthful skin, cell health, elasticity, and flexibility
because of its antioxidant effect to bond with collagen(37).
According to Dr. Bojanowski K., grape seed extract may have a potential in anti-aging effects
throughout all skin compartments, including dermal and epidermal layers because of its induced signal
transduction pathways in facial hypodermis(38). In a study of a total of men from 35 to 60 years of age,
phototypes I to III, indictaed a positive effect in counteract skin photoaging, in daily application of
mixture containing lycopene, acerola extract, grape seed extract and Biomarine ComplexT(39).

15. Lavender Lavender is a flower plant of the genus Lavandula, belonging to the family Lamiaceae,
native to Asia. The herb has been used in traditional medicine to treat painful bruises and aches,
 to relieve various neuralgic pains, sprains, rheumatism, etc.
Suggestion of Lavender aromatherapy may potentiate to ease anxiety in patients undergoing minimally
invasive facial cosmetic procedures(40).
In photodegradation and photooxidation, chemical composition and bioactive properties of Lavandula
angustifolia Miller essential oil, used conjunction with bee oglue showed that bee glue expresses a
highly protected lavender oil secondary metabolites from degradation and also preserved their
antiradical properties, both in in vitro antioxidant assays and in cell oxidative damage evaluations(41).

16. Huang Qi (Radix astragali) Huang Qi or Bei Qi is also known as Astragalus root. The sweet herb
 has been used as diuretic agent and to lower blood pressure, increase blood pressure, lessens
proteinuria, improve endurance, protect liver function, regulate blood sugar, etc. as it tonifies Qi,
raises Yang, strengthens the Defensive-Qi and the Exterior, expels toxins, etc. by enhancing the
functions of lung and spleen channels.
The study of non-fermented (HQNB) and fermented preparations (HQB) of Radix astragali on
hyaluronic acid (HA) production in primary human skin cells, showed that HQB significantly
stimulated HA production in both cultured primary human epidermal keratinocytes and human dermal
fibroblasts and  increased the expression of hyaluronan synthase 3 and hyaluronan synthase 2 mRNA
in HaCaT cells and human fibroblasts, respectively in dose-dependent manners(42).

17. Puerariae Radix (Ge Gen)
Ge Gen is also known as Kudzuvine Root. The acrid, sweet and neutral herb has been used in TCM as
anti-arrhythmia, anti cancers, anti-oxidation, anti platelet coagulation, etc. and to lower blood sugar,
relax the blood vessels, improve memory, treat diarrhea, etc., as it raises Yang; clears Heat,
promotes generation of Body Fluids, etc., by enhancing the functions of spleen and stomach channels.
The study of the effect of Puerariae Radix (PR), a Chinese herb and a popular food in Asia in
Hyaluronic acid (HA) concentrations in the intercellular spaces of the epidermis and the
connective tissues of the dermis, showed to stimulate the HA production of normal human epidermal
keratinocytes (NHEK), in dose-dependent, due to its rich in isoflavone glycosides like genistin and
daidzin(43).

20. Labisia pumila (Kacip Fatimah) Labisia pumila is the henus Lobisia, belonging to the family belongs to the family of Myrsinaceae
native to in Southeast Asia, particularly Malaysia, Indonesia, Thailand, Laos, Cambodia, and Vietnam.
In skin aging, phytochemicals found in the herbal extract found in Labisia pumila, protected against
natural aging process and accelerated by UV radiation through promoting the production of skin
collagen synthesis(43) and attenuation of UVB-induced MMP-9 expression in phtoaging(44).

Taken altogether, certain herbs have been found to enhance the protection of skin against natural
aging through protection in the degradation of epidermal and dermal layers of the extracellular
matrix (ECM), via their antioxidant and stimulative effects. Futher studies are necessary to identify
 theirs effective ingredients to improve the clincal vadilation. As always all articles
written by Kyle J. Norton are for information & education only, please consult your Doctor & Related
field specialist before applying.

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References
(a) Skin ageing: natural weapons and strategies by Binic I¹, Lazarevic V, Ljubenovic M, Mojsa J, Sokolovic D.(PubMed)
(b) Phytoconstituents as photoprotective novel cosmetic formulations by Saraf S¹, Kaur CD.(PubMed)
(c) Differential expression of cathepsins K, S and V between young and aged Caucasian women skin epidermis by Sage J¹, De Quéral D², Leblanc-Noblesse E², Kurfurst R², Schnebert S², Perrier E², Nizard C², Lalmanach G³, Lecaille F⁴.(PubMed)
(d) Bioactive compounds from natural resources against skin aging by Mukherjee PK¹, Maity N, Nema NK, Sarkar BK.(PubMed)
(1) Dietary Aloe Vera Supplementation Improves Facial Wrinkles and Elasticity and It Increases the Type I Procollagen Gene Expression in Human Skin in vivo by Cho S¹, Lee S, Lee MJ, Lee DH, Won CH, Kim SM, Chung JH.(PubMed)
(2) Dry skin in the elderly: complexities of a common problem by White-Chu EF¹, Reddy M.(PubMed)
(3) [The protective effects of sodium selenite and aloin against ultraviolet A radiation].

[Article in Chinese]by Guo Y¹, Ji R, Lü X, Wan YF, Jiang X.(PubMed)

(4) Green tea extract protects human skin fibroblasts from reactive oxygen species induced necrosis by Silverberg JI¹, Jagdeo J, Patel M, Siegel D, Brody N.(PubMed)

(5) Tannase-converted green tea catechins and their anti-wrinkle activity in humans by Hong YH¹, Jung EY, Shin KS, Yu KW, Chang UJ, Suh HJ.(PubMed)

(6) The use of green tea extract in cosmetic formulations: not only an antioxidant active ingredient by Gianeti MD¹, Mercurio DG, Campos PM.(PubMed)

(7) Human skin safety test of green tea cell extracts in condition of allergic contact dermatitis by Kim HK¹, Choi SY, Chang HK, Baek SY, Chung JO, Rha CS, Kim BJ, Kim MN.(PubMed)

(8) Combined topical application of lotus and green tea improves facial skin surface parameters by Mahmood T¹, Akhtar N.(PubMed)

(9) Design and in vivo evaluation of emulgel formulations including green tea extract and rose oil by Yapar EA, Ynal O, Erdal MS.(PubMed)

(10) Korean Red Ginseng Tonic Extends Lifespan in D. melanogaster by Kim MS.(PubMed)
(11) Effects of red ginseng extract on UVB irradiation-induced skin aging in hairless mice by Kang TH¹, Park HM, Kim YB, Kim H, Kim N, Do JH, Kang C, Cho Y, Kim SY.(PubMed)
(12) Enzyme-processed Korean Red Ginseng extracts protects against skin damage induced by UVB irradiation in hairless mice by Hwang E¹, Sun ZW, Lee TH, Shin HS, Park SY, Lee DG, Cho BG, Sohn H, Kwon OW, Kim SY, Yi TH.(PubMed)
(13) Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver by Kim DH¹, Chung JH, Yoon JS, Ha YM, Bae S, Lee EK, Jung KJ, Kim MS, Kim YJ, Kim MK, Chung HY.(PubMed)
(14) Hormesis-based anti-aging products: a case study of a novel cosmetic by Rattan SI¹, Kryzch V, Schnebert S, Perrier E, Nizard C.(PubMed)
(15) Fermenting red ginseng enhances its safety and efficacy as a novel skin care anti-aging ingredient: in vitro and animal study by Lee HS¹, Kim MR, Park Y, Park HJ, Chang UJ, Kim SY, Suh HJ.(PubMed)

(16) Inhibitory effect of encapsulated curcumin on ultraviolet-induced photoaging in mice by Agrawal R¹, Kaur IP.(PubMed)
(17) Bioactive compounds from natural resources against skin aging by Mukherjee PK¹, Maity N, Nema NK, Sarkar BK.(PubMed)
(18) Curcumin induces heme oxygenase-1 in normal human skin fibroblasts through redox signaling: relevance for anti-aging intervention by Lima CF¹, Pereira-Wilson C, Rattan SI.(PubMed)
(19) Titrated extract of Centella asiatica provides a UVB protective effect by altering microRNA expression profiles in human dermal fibroblasts by An IS¹, An S, Kang SM, Choe TB, Lee SN, Jang HH, Bae S.(PubMed)
(20) Centella asiatica protects against UVB-induced HaCaT keratinocyte damage through microRNA expression changes by An IS¹, An S, Choe TΒ, Kang SΜ, Lee JH, Park IC, Jin YW, Lee SJ, Bae S.(PubMed)
(21) Evaluation of the effects of a preparation containing asiaticoside on periocular wrinkles of human volunteers by Lee J¹, Jung E, Lee H, Seo Y, Koh J, Park D.(PubMed)
(22) Improving lip wrinkles: lipstick-related image analysis by Ryu JS¹, Park SG, Kwak TJ, Chang MY, Park ME, Choi KH, Sung KH, Shin HJ, Lee CK, Kang YS, Yoon MS, Rang MJ, Kim SJ.(PubMed)
(23) [Comparative activity of asiaticoside and madecassoside on type I and III collagen synthesis by cultured human fibroblasts].[Article in French] by Bonté F¹, Dumas M, Chaudagne C, Meybeck A.(PubMed)(24) Anti-wrinkle activity of ziyuglycoside I isolated from a Sanguisorba officinalis root extract and its application as a cosmeceutical ingredient by Kim YH¹, Chung CB, Kim JG, Ko KI, Park SH, Kim JH, Eom SY, Kim YS, Hwang YI, Kim KH.(PubMed)
(25) Inhibitory effect of an extract of Sanguisorba officinalis L. on ultraviolet-B-induced photodamage of rat skin by Tsukahara K¹, Moriwaki S, Fujimura T, Takema Y.(PubMed)
(26) Magnolia ovovata extract and its active component magnolol prevent skin photoaging via inhibition of nuclear factor kappaB by Tanaka K¹, Hasegawa J, Asamitsu K, Okamoto T.(PubMed)
(27) Protecting skin photoaging by NF-kappaB inhibitor by Tanaka K¹, Asamitsu K, Uranishi H, Iddamalgoda A, Ito K, Kojima H, Okamoto T.(PubMed)
(28) Protective effect of detoxified Rhus verniciflua stokes on human keratinocytes and dermal fibroblasts against oxidative stress and identification of the bioactive phenolics by Liu CS¹, Nam TG, Han MW, Ahn SM, Choi HS, Kim TY, Chun OK, Koo SI, Kim DO.(PubMed)
(29) Identification of Rhus verniciflua Stokes compounds that exhibit free radical scavenging and anti-apoptotic properties by Lee JC¹, Lim KT, Jang YS.(PubMed)
(30) Bioactive compounds from natural resources against skin aging by Mukherjee PK¹, Maity N, Nema NK, Sarkar BK.(PubMed)
(31) The active natural anti-oxidant properties of chamomile, milk thistle, and halophilic bacterial components in human skin in vitro by Mamalis A¹, Nguyen DH, Brody N, Jagdeo J.(PnbMed)
(32) Effect of a novel dietary supplement on skin aging in post-menopausal women by Skovgaard GR¹, Jensen AS, Sigler ML(PubMed)
(33) Cinnamon extract promotes type I collagen biosynthesis via activation of IGF-I signaling in human dermal fibroblasts by Takasao N¹, Tsuji-Naito K, Ishikura S, Tamura A, Akagawa M.(PubMed)
(34) Clinical efficacy comparison of anti-wrinkle cosmetics containing herbal flavonoids by Chuarienthong P¹, Lourith N, Leelapornpisid P.(PubMed)
(35) Green tea and the skin by Hsu S.(PubMed)
(36) Biochemical studies of a natural antioxidant isolated from rosemary and its application in cosmetic dermatology by Calabrese V¹, Scapagnini G, Catalano C, Dinotta F, Geraci D, Morganti P.
(PubMed)
(37) enolics in grape seeds-biochemistry and functionality by Shi J¹, Yu J, Pohorly JE, Kakuda Y.by (PubMed)
(38) Hypodermal delivery of cosmetic actives for improved facial skin morphology and functionality by Bojanowski K.(PubMed)
(39)Clinical, biometric and ultrasound assessment of the effects of daily use of a nutraceutical composed of lycopene, acerola extract, grape seed extract and Biomarine Complex in photoaged human skin by Costa A¹, Lindmark L, Arruda LH, Assumpção EC, Ota FS, Pereira Mde O, Langen SS.(PubMed)
(40) Effects of lavender olfactory input on cosmetic procedures by Grunebaum LD¹, Murdock J, Castanedo-Tardan MP, Baumann LS.(PubMed)
(41) Biochemical Composition and Antioxidant Properties of Lavandula angustifolia Miller Essential Oil are Shielded by Propolis Against UV Radiations by Angelo G¹, Lorena C, Marta G, Antonella C.(PubMed)
(42) Stimulating effects of Bacillus subtilis natto-fermented Radix astragali on hyaluronic acid production in human skin cells by Hsu MF¹, Chiang BH.(PubMed)
(43) Comparison of Puerariae Radix and its hydrolysate on stimulation of hyaluronic acid production in NHEK cells by Wen KC¹, Lin SP, Yu CP, Chiang HM.(PubMed)
(44) eview on Labisia pumila (Kacip Fatimah): bioactive phytochemicals and skin collagen synthesis promoting herb by Chua LS¹, Lee SY, Abdullah N, Sarmidi MR.(PubMed)
(45) Labisia pumila extract protects skin cells from photoaging caused by UVB irradiation by Choi HK¹, Kim DH, Kim JW, Ngadiran S, Sarmidi MR, Park CS.(PubMed)

Ovarian Cancer in B6 Points of View

 Kyle J. Norton(Draft Article)

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovarian cells,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.

Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some vitamins have showed to inhibit the progression of cancer with little or no side effects.
Vitamin B6, also known as pyridoxine, is a water soluble vitamin found abundantly in green peas, yams, broccoli, asparagus and turnip greens,Peanuts, sunflower seeds, cashews and hazelnuts, meat, fish etc., with functions of amino acid, carbohydrate  metabolism, brain health, and liver detoxification, etc.

Epidemiological studies, linking vitamin B6 in reduced risk of ovarian cancer have been inconsistent. 
The study of the Brigham and Women's Hospital, Boston, indicated intake of one-carbon metabolism related nutrients, especially vitamin B(6) and methionine, may lower ovarian cancer risk (1). In 80,254 Nurses' Health Study participants, during 22 years of follow-up (1980-2002), researchers found little evidence to support dietary folate, methionine, and vitamin B(6) in related ovarian cancer risk(2), But
in the study to compare the effectiveness of acupuncture plus vitamin B6 PC6 points injection with acupuncture or vitamin B6 alone in controlling emesis of 142 patients, between March 1, 2006, and June 30, 2008 indicated that acupuncture plus vitamin B6 PC6 points injection with acupuncture relieved nausea and vomiting in patients with ovarian cancer, undergoing a highly emetogenic chemotherapy regimen(3). In a  total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) conducted by the Albert Einstein Cancer Center, showed that although  administration of pyridoxine significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with  cisplatin (DDP) and hexamethylmelamine (HMM) regimens(4). In the assessed dietary intakes and factors associated with diet in women with family history of breast and/or ovarian cancer (FHBOC) study, suggest that women with FHBOC should be encouraged to meet dietary guidelines for cancer prevention, including intake of vitamin B6(5).

Taking altogether, vitamin B6 may be associated to reduced risk and treatment of ovarian cancer when it is used in conjunction with acupuncture, but further study with large sample and multi center studies are necessary to improve the validation. Over doses may induced the symptoms of difficulty coordinating movement, numbness, sensory changes, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

 
References
(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M¹, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A¹, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E¹, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM¹, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1)Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR¹, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)
(2) Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer by Tworoger SS¹, Hecht JL, Giovannucci E, Hankinson SE.(PubMed)

(3) Vitamin B6 points PC6 injection during acupuncture can relieve nausea and vomiting in patients with ovarian cancer by You Q¹, Yu H, Wu D, Zhang Y, Zheng J, Peng C.(PubMed)
(4) Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group by Wiernik PH¹, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J.(PubMed)
(5)
(6) Diet and predictors of dietary intakes in women with family history of breast and/or ovarian cancer by McEligot AJ¹, Mouttapa M, Ziogas A, Anton-Culver H.(PubMed)




 

Ovarian Cancer in Vitamin K Points of View

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovaries,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.

Researchers at the Showa University indicated that vitamin K may process the anti wide array of human cancer cell lines properties through differentiation and apoptosis(1). DR. Shibayama-Imazu, The leader of the research team said that these inductions may be through interruption of the morphological changes and DNA fragmentation via the loss of mitochondrial membrane potential (DeltaPsim caused by superoxide(1).  Vitamin K2 also induced apoptosis of human ovary cancer cells (TYK-nu cells), through the process of production of superoxide, induced oxidative stress in mitochondria might damage mitochondrial membranes(2). In PA-1 ovarian cancer cells, vitamin exhibited apoptosis through increased in the synthesis of TR3 and the accumulation of TR3 in mitochondria and in nuclei via a JNK signaling pathway(3). Against human ovarian carcinoma cell line (MDAH 2774), the composition of VC (ascorbic acid) and VK3 (menadione), inhibited cell proliferation through DNA degradation(4) and exposure to the composition also expressed the anti proliferation of cell death through autoschizis (43%), apoptosis (3%), and oncosis (1.9%)(5). In the comparison of the effect of vitamin K(2) (menaquinone 4) and  geranylgeraniol (GGO)inhuman cancer cell line, showed that GGO inhibited the growth of all eight cell lines derived from solid tumors, while vitamin K(2) selectively inhibited the proliferation and induced apoptosis in both ovarian cell lines(6). Study of the cytotoxic effect and mechanism of action of vitamins C (VC) and K3 (VK3) on ovarian carcinoma, indicated a positive effects of the composition in induced cell death  (displayed characteristics of both apoptosis and necrosis), through cycle arrest and degradation of chromosomal DNA(7).

Taking all together, vitamin VK2 and VK3 found effectively in reduced risk and treatment of ovarian cancer through activation of cell death mechanism, via activation of RSO, cell cycle arrest,  and degradation of DNA. Large sample and multi centers studies to validate this effectiveness. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies

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References
(1) Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential. by Shibayama-Imazu T¹, Aiuchi T, Nakaya K. (PubMed)
(2) Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K2 trigger apoptosis in human ovarian cancer TYK-nu cells by Shibayama-Imazu T¹, Sonoda I, Sakairi S, Aiuchi T, Ann WW, Nakajo S, Itabe H, Nakaya K.(PubMed)
(3) Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei by Sibayama-Imazu T¹, Fujisawa Y, Masuda Y, Aiuchi T, Nakajo S, Itabe H, Nakaya K.(PubMed)
(4) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation by Gilloteaux J¹, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL.(PubMed)
(5) Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitamin C:K3 treatment by Gilloteaux J¹, Jamison JM, Arnold D, Taper HS, Von Gruenigen VE, Summers JL.(PubMed)
(6) Vitamin K(2) selectively induced apoptosis in ovarian TYK-nu and pancreatic MIA PaCa-2 cells out of eight solid tumor cell lines through a mechanism different from geranylgeraniol by Shibayama-Imazu T¹, Sakairi S, Watanabe A, Aiuchi T, Nakajo S, Nakaya K.(PubMed)
(7) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma by von Gruenigen VE¹, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, Summers JL.(PubMed)