Kyle J. Norton(Scholar and Master of Nutrients, all right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
Oleanolic acid
Oleanolic acid is a phytochemincal in the subclass of Triterpenoid, belonging to the group of Terpenes found abundantly in honey mesquite, garlic, java apple, clove, etc.
Health Benefits
1. Anti inflammatory effects
In the investigation by monitoring the effect of OA on lipopolysaccharide (LPS)-mediated release of HMGB1 and the HMGB1-mediated modulation of inflammatory responses in human umbilical vein endothelial cells (HUVECs), showed that OA potently inhibited the release of HMGB1 by HUVECs as well as down-regulated HMGB1-dependent adhesion and migration of the monocytic cell line THP-1 to activated HUVECs. OA also down-regulated the cell surface expression of the receptor of HMGB1, thereby inhibiting HMGB1-dependent pro-inflammatory responses by inhibiting activation of nuclear factor-κB (NF-κB) and production of tumor necrosis factor-α (TNF-α) by HMGB1, according to "Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs" by Yang EJ, Lee W, Ku SK, Song KS, Bae JS.(1)
2. Anti tumors effects
In the examination of the anti tumor effect of a new oleanolic triterpene, 3β,6β,19α-trihydroxy-12-oleanen-28-oic acid (1) obtained from the chloroform-soluble portion of the 90% alcohol-water extract of the stem bark of Uncaria macrophylla, found that as the cytotoxicities of the compound was evaluated against two cancer cell lines of MCF-7 and HepG2 by the MTT method, and the compound exhibited weak activities with the IC(50) values of 78.2 µg/mL and 73.9 µg/mL, according to "A New Triterpene From Uncaria macrophylla and Its Antitumor Activity" by Sun G, Zhang X, Xu X, Yang J, Zhong M, Yuan J.(2)
3. Non-small cell lung cancer
In the evaluation of wheather oleanolic acid (OA), a pentacyclic triterpene present in several plants, is able to circumvent the mechanisms of drug resistance present in non-small cell lung cancer (NSCLC) cell lines and to induce their death, indicated that the data provide a significant insight into the antitumoral and antimetastatic activity of OA in NSCLC and suggest that including OA in the NSCLC regimens may help to decrease the number of relapses and reduce the development of metastases, according to "Oleanolic acid initiates apoptosis in non-small cell lung cancer cell lines and reduces metastasis of a B16F10 melanoma model in vivo" by Lúcio KA, Rocha Gda G, Monção-Ribeiro LC, Fernandes J, Takiya CM, Gattass CR.(3)
4. Ovarian cancer
In the observation of the anticancer activity of methyl-2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oate (CDDO-Me) derived from CDDO, a synthetic analog of oleanolic acid, and its mechanism of action in killing of human ovarian cancer cells, found that CDDO-Me strongly inhibited the growth of ovarian cancer cells by inducing apoptosis characterized by increased annexin V binding, cleavage of poly (ADP-ribose) polymerase (PARP-1) and procaspases-3, -8 and -9. In addition, CDDO-Me induced mitochondrial depolarization, according to "Synthetic oleanane triterpenoid, CDDO-Me, induces apoptosis in ovarian cancer cells by inhibiting prosurvival AKT/NF-κB/mTOR signaling" by Gao X, Liu Y, Deeb D, Arbab AS, Guo AM, Dulchavsky SA, Gautam SC.(4)
5. Prostate Cancer
In the deternimation of the efficacy of 2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), a synthetic analog of oleanolic acid, and its C28 methyl ester derivative (CDDO-Me in preventing the development and progression of prostate cancer in the transgenic adenocarinoma of the mouse prostate (TRAMP) model, showed that treatment with CDDO-Me inhibited the expression of prosurvival p-Akt and NF-κB in the prostate and knocking-down Akt in TRAMPC-1 tumor cells sensitized them to CDDO-Me. These findings indicated that Akt is a target for apoptoxicity in TRAMPC-1 cells in vitro and potentially a target of CDDO-Me for inhibition of prostate cancer in vivo, according to 'Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer" by Gao X, Deeb D, Liu Y, Arbab AS, Divine GW, Dulchavsky SA, Gautam SC.(5)
6. Multi-drug resistance cancers
In the study of the proliferation-inhibiting and apoptosis-inducing effects of ursolic acid (UA) and oleanolic acid (OA) on multi-drug resistance (MDR) cancer cells in vitro, indicated that Both UA and OA have antitumor effects on cancer cells with MDR, and the optimal effect is shown by UA on colonic cancer cells. Also, UA shows cell apoptosis-inducing effect on SW480, possibly by way of down-regulating the expressions of apoptosis antagonistic proteins, Bcl-2, Bcl-xL, and surviving, according to "Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro" by Shan JZ, Xuan YY, Ruan SQ, Sun M.(6)
7. Pancreatic Cancer
In the evaluation of the antitumor activity and the mechanism of action of methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me), a oleanane-derived synthetic triterpenoid for human pancreatic cancer cell lines, found that CDDO-Me inhibited the growth of both K-ras mutated (MiaPaca2, Panc1 and Capan2) and wild-type K-ras (BxPC3) pancreatic cancer cells at very low concentrations. The growth inhibitory activity of CDDO-Me was attributed to the induction of apoptosis characterized by increased annexin-V-FITC binding and cleavage of PARP-1 and procaspases-3, -8 and-9. In addition, CDDO-Me induced the loss of mitochondrial membrane potential and release of cytochrome C. The antitumor activity of CDDO-Me was associated with the inhibition of prosurvival p-Akt, NF-κB and mammalian target of rapamycin (mTOR) signaling proteins and the downstream targets of Akt and mTOR, such as p-Foxo3a (Akt) and p-S6K1, p-eIF-4E and p-4E-BP1 (mTOR), according to "CDDO-Me: A Novel Synthetic Triterpenoid for the Treatment of Pancreatic Cancer" by Deeb D, Gao X, Arbab AS, Barton K, Dulchavsky SA, Gautam SC.(6)
7. Colorectal cancer
In the study of the role of free radicals in the growth inhibitory and apoptosis-inducing activity of CDDO-Me in colorectal cancer cells lines, found that CDDO-Me potently inhibited the growth of colorectal cancer cells and pretreatment of cancer cells with small-molecule antioxidant N-acetylcysteine (NAC) completely blocked the growth inhibitory activity of CDDO-Me. CDDO-Me caused the generation of reactive oxygen species, which was inhibited by NAC and mitochondrial chain 1 complex inhibitors DPI and rotenone. CDDO-Me induced apoptosis as demonstrated by the cleavage of PARP-1, activation of procaspases -3, -8, and -9 and mitochondrial depolarization and NAC blocked the activation of these apoptosis related processes, according to "Role of reactive oxygen species (ROS) in CDDO-Me-mediated growth inhibition and apoptosis in colorectal cancer cells" by Gao X, Deeb D, Liu P, Liu Y, Arbab-Ali S, Dulchavsky SA, Gautam SC.(7)
8. Neuroinflammatory disorders
In the demonstration of the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes, founm that CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of pro-inflammatory transcripts with concomitant induction of anti-inflammatory genes including Ptgds and Hsd11b1, according to "Triterpenoid modulation of IL-17 and Nrf-2 expression ameliorates neuroinflammation and promotes remyelination in autoimmune encephalomyelitis" by Pareek TK, Belkadi A, Kesavapany S, Zaremba A, Loh SL, Bai L, Cohen ML, Meyer C, Liby KT, Miller RH, Sporn MB, Letterio JJ.(8)
9. Antibiotic resistance
In the investigation of antibiotic resistance effects of oleanolic acid (OA) and ursolic acid (UA), among bacterial pathogens (Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus and Staphylococcus epidermidis), found that Using FICI value estimation and the time-kill method it was demonstrated that in some combinations, the tested compounds acted in synergy to lower the susceptibility of S. aureus, S. epidermidis and L. monocytogenes to ampicillin and oxacillin, but no synergy was observed for P. aeruginosa, according to "Modulation of antibiotic resistance in bacterial pathogens by oleanolic acid and ursolic acid" by Kurek A, Nadkowska P, Pliszka S, Wolska KI.(9)
10. Skin fibroblast cells
In the observation of how ursolic and oleanolic acids can be used for the purpose of quality control of natural products used in dermatocosmetology as well as of various other therapeutic preparations, showed that Of the two isomeric compounds, UA showed a higher cytotoxic activity against HSF cells than did OA. Our investigations showed that OA, in view of its non-toxic nature, may be used as a supplementary factor for dermal preparations, according to "The effect of ursolic and oleanolic acids on human skin fibroblast cells" by Wójciak-Kosior M, Paduch R, Matysik-Woźniak A, Niedziela P, Donica H.(10)
11. Diabetic nephropathy
In the investigation of the effect of a herbomineral formulation (HMF) on early diabetic nephropathy, indicated that our experimental findings clearly demonstrate that HMF has an ability to prevent the progression of early diabetic nephropathy. Such protective effect of HMF might be due to the presence of flavonoids (catechin, quercetin, rutin) and triterpene saponins (oleanolic acid and gymnemic acid) which are known to possess potent antioxidant properties, according to "Protective effect of herbomineral formulation (Dolabi) on early diabetic nephropathy in streptozotocin-induced diabetic rats' by Baig MA, Gawali VB, Patil RR, Naik SR.(11)
12. Antihypertensive, antiatherosclerotic, insulin resistanceand antioxidant activity
In the study of triterpenoids isolated of the African wild olive leaves (AO) used in the experiments was found to contain 0.27% 1:1 mixture of oleanolic acid and ursolic acid, named oleuafricein and of Greek olive leaves (GO) found to contain 0.71% oleanolic acid, and the Cape Town cultivar (CT) contained 2.47% oleanolic acid. No ursolic acid was found in either GO or CT.
found that Aal three isolates, in a dose 60 mg/kg b.w. for 6 weeks treatment, prevented the development of severe hypertension and atherosclerosis and improved the insulin resistance of the experimental animals. GO, OA and CT isolates could provide an effective and cheap treatment of this particular, most common type of salt-sensitive hypertension in the African population, according to "Antihypertensive, antiatherosclerotic and antioxidant activity of triterpenoids isolated from Olea europaea, subspecies africana leaves" by Somova LI, Shode FO, Ramnanan P, Nadar A.(12)
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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22386814
(2) http://www.ncbi.nlm.nih.gov/pubmed/22334066
(3) http://www.ncbi.nlm.nih.gov/pubmed/22174843
(4) http://www.ncbi.nlm.nih.gov/pubmed/22110186
(5) http://www.ncbi.nlm.nih.gov/pubmed/21961053
(6) http://www.ncbi.nlm.nih.gov/pubmed/21799944
(7) http://www.ncbi.nlm.nih.gov/pubmed/21699019
(8) http://www.ncbi.nlm.nih.gov/pubmed/22355716
(9) http://www.ncbi.nlm.nih.gov/pubmed/22341643
(10) http://www.ncbi.nlm.nih.gov/pubmed/22252762
(11) http://www.ncbi.nlm.nih.gov/pubmed/22116744
(12) http://www.ncbi.nlm.nih.gov/pubmed/12648829
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