Shingles

I. Shingles also known as herpes zoster or zona is defined as a viral disease with condition of a painful, blistering skin rash on one side of the body of  that can continue to be painful even after the rash have long disappeared(1), as a result of varicella-zoster viral causes of a nerve and skin inflammation.

II. Symptoms
1. Headache
There is a report of a 60-year-old man presented after burning the roof of his mouth on hot soup five days earlier. The burned sensation resolved after one day; however, a couple of days later, he noticed tingling on the right side of the hard palate that progressed to a scalded sensation. This was accompanied by tenderness along the right temporal area and discomfort below the right ear. He denied a history of oral lesions. Doctors in the  Mayo Clinic, the presence of multiple vesicles that vary in size and are confined to the right side of the hard palate (i.e., cranial nerve V2 distribution) accompanied by neuralgia and erythema in ipsilateral cutaneous portions of the right trigeminal nerve suggests herpes zoster over oral herpes simplex virus (HSV) infection(2).

2. Other symptoms
Dr. Goh CL, and Dr. Khoo L. at the Institute of Dermatology, National Skin Center, in a retrospective study of the epidemiology and morbidity of herpes zoster and the risk factors for herpes zoster morbidity in Singapore,  suggested that The common presenting symptoms were pain (90%), feelings of helplessness and depression (20%), and flu-like symptoms (12%). The commonest prodromes were pain (41%), itching (27%), and paresthesia (12%).  Pain was experienced by almost all (95%) patients during the course of their disease. It tended to be more severe in older patients. Burning (26%), stabbing (15%), and shooting (15%) pain were the most common types experienced. Post-herpetic neuralgia was significantly more common in older patients. The prevalence of post-herpetic neuralgia decreased over time in all age groups. A higher proportion of older patients (more than 50 years of age) (20%) suffered from post-herpetic neuralgia compared with younger patients (less than 30 years of age) (7%) (not significant). Patients in all age groups considered acute pain (46%) and persistent pain (25%) to be their most unbearable symptoms during the course of herpes zoster. The most significant problems caused by herpes zoster pain were insomnia (25%), misery (feeling helpless and depressed) (20%), limitation of movement (9%), and inability to continue work (8%).(3)


3. Not all patients with herpes zoster adjacent to the eye will develop ocular involvement, but in those that do, there can be a wide variety of manifestations
a. Eyelid with Rash and vesicles in acute case and Scarring, loss of lashes in chronic case
b. Conjunctiva with Conjunctivitis in acute case
c. Cornea with Corneal ulcers in acute case and Corneal inflammation and scarring, loss of corneal sensation in chronic case.
d. Retina with Retinitis in acute case and Cystoid macular edema (swelling of the central retina) in chronic case
e. Etc.(4)

III. Causes and risk factors
A, Risk factors
Although shingles can occur in anyone exposed to the varicella-zoster virus, people with
Advanced age and A weakened immune system are at increased risk of shingles and post
1. Advanced age
In the sane above study, Dr. Goh CL, and Dr. Khoo L. at the Institute of Dermatology, National Skin Center also said that pain was experienced by almost all (95%) patients during the course of their disease. It tended to be more severe in older patients. Burning (26%), stabbing (15%), and shooting (15%) pain were the most common types experienced. Post-herpetic neuralgia was significantly more common in older patients.(3)

2. Weakened immune system
Newborns, pregnant women, those over 50, and those with a weakened immune system (from another disease like HIV or cancer, for example), are more likely to be susceptible to the Varicella-Zoster virus as well as complications from either the Chicken Pox or Shingles.(5). Other report that Children infrequently are afflicted with herpes zoster (HZ). Activation of latent varicella-zoster virus (VZV) in a partially immune host results in HZ. Herpes zoster in children can be benign or with varied severity, especially in cases associated with malignancy. Because of its rarity, we report widespread multisegmental HZ primarily presenting on the right side of the body and abdomen in a 6-year-old immunocompetent girl.(6)

3. Etc.

B. Causes 
Causes of Shingles is as a result of a nerve and skin inflammation with zoster virus (VZV). After having chickenpox, the virus lives dormant in the nervous system and is never fully cleared from the body. Under certain circumstances, such as weakened immune system, the virus travels up the nerve roots to the area of skin supplied by those specific nerve roots.

III. Stages of Shingles
Shingles can be classified in 5 stages
1. The First Shingles Stage: Chickenpox
People who has developed Chickenpox have an increased risk of  shingles later in their life, as the virus can live dormant in the nervous system and is never fully cleared from the body. Dr. Welsby PD. at the Infectious Diseases Unit, Western General Hospital, Edinburgh EH4 2XU, UK. indicated that Chickenpox in the United Kingdom, where vaccination is not undertaken, has had a stable epidemiology for decades and is a routine childhood illness. In the UK vaccination is not done because introduction of a routine childhood vaccination might drive up the age at which those who are non-immune get the illness (chickenpox tends to be more severe the older you are), and the incidence of shingles may increase(7).

2. The Second Shingles Stage: Varicella-zoster viral Reactivation
Under certain circumstance, most of the time under weakened immune system as we age or other health conditions or as a result of other medication, the varicella virus can reactivate, triggering the development of shingles.

3. The Third Shingles Stage: Rash
This is the painful stage of shingle as in the earliest stages, patches of bumpy red blisters erupt on your skin and continue for 7 to 10 days.

4. The Fourth Shingles Stage: Crusting
After 7 to 10 days, the blisters begin to fall off that can lead to irregular skin pigmentation of which can be temporary  but in severe cases it can be permanent.

5. The Fifth Shingles Stage: Postherpetic Neuralgia
Postherpetic neuralgia is the pain that lasts for more than a month after infection of shingles, but in some cases it can be last for months or years. The incidence of shingles increases with age and immunosuppression. Guidelines for managing shingles are now available and implementation, with the emphasis on early treatment, may reduce the severity of a shingles attack and reduce the incidence of complications.

IV. Complications
1. Anterior uveitis
In the study to investigate the relationship between herpes zoster (HZ) and the subsequent risk of anterior uveitis during the year following an HZ diagnosis, Dr. Wang TJ, and the team at the Taipei Medical University suggested that The risk of anterior uveitis increased in the year following a diagnosis of HZ. and suggest that patient eye condition be evaluated following diagnosis with HZ(8).

2. Stroke
In the study to investigate the risk of stroke development following a diagnosis of herpes zoster ophthalmicus (HZO), Dr. Lin HC and the team at the Taipei Medical University Hospital herpes zoster ophthalmicus may represent a marker of increased risk of stroke development during the 1-year follow-up period(9).

3. Occipital neuralgia
Paroxysmal shooting or stabbing pain in the dermatomes of the nervus occipitalis major or nervus occipitalis minor is defined as occipital neuralgia. The initial cause of the neuralgia appears to be from inflammation, damage or irritation of these nerves. In this article, we present a patient with occipital neuralgia followed by thoracic herpes lesion(10).

4. Bullous Variant of Sweet's Syndrome 
Dr. Yuichiro Endo, and the researcher team at the Department of Dermatology, Kyoto University, Kyoto, reported a case of a 75-year-old male presented to our department with haemorrhagic and erosive plaques on the left side of the face and neck. After discussion they said that our case was unique in that herpes zoster virus infection seemed to trigger the development of bullous variant of SS. We think the preceding blisters were not caused by SS, but rather by the herpes zoster virus infection because the initial lesion subsided when SS progressed(11).

5. Etc.

IV. Diagnosis
Diagnosis are depending to the rash location if it is in one side of the body and erupts along one of the many nerve paths in cells of the dorsal root ganglion with the emphasis on early treatment, may reduce the severity of a shingles attack and reduce the incidence of complications. The confirmation of the diseases may be included sharp and burning pain, history of chickenpox or chickenpox vaccinr, the patient is over 50 years of age, etc.
Other researchers supported the potential of developing FTIR microspectroscopy as a simple, reagent free method for the early detection and accurate differentiation of different stages during the development of herpes virus infection(12)

V. Prevention
A. The Do's and Do not's list 
1. Unhealthy diet
Unhealthy diet such as American typical diet can cause imbalance of nutrients in the body of that can lead to nutrient deficiencies with excessed fat building up. Aging is associated with declined immune function, particularly T cell-mediated activity, which contributes to increased morbidity and mortality from infectious disease and cancer in the elderly. Studies have shown that nutritional intervention may be a promising approach to reversing impaired immune function and diminished resistance to infection with aging(13) of that can lead to immune deficiency causes of shingle.

2. Smoking
Even though there are no direct evidence the smoking can caused increased risk of shingle, but some researchers suggested that there is an association between cigarette smoking and the depression of immune function by studies of 35 subjects before, and three months after, they had ceased to smoke cigarettes. The studies included tests of natural killer cell (NK) activity against several target cells and the measurement of immunoglobulin levels in sera and saliva. Similar tests were conducted on 29 control subjects who continued to smoke. The results indicated a significant decrease in lymphocyte counts and a significant increase in NK activity against cultured melanoma cells in subjects who ceased smoking(14)

3. Excessive alcohol drinking
Long-term alcohol consumption leads to altered inflammatory cell and adaptive immune responses with associated pathologies and increased incidence of infections(15). 

4. Take your vaccine
The zoster vaccine was approved by the US Food and Drug Administration in 2006 and is indicated for prevention of herpes zoster in immunocompetent persons aged 60 years and older. The herpes zoster vaccine provides physicians with an effective means for reducing a patient's risk for developing shingles and its attendant complications. No significant safety concerns regarding the vaccine have been identified. Indications for use of the attenuated-virus vaccine in special subpopulations continue to evolve(16). Others suggested that Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and severity than placebo recipients who developed herpes zoster. Zoster vaccine had continuing efficacy in a Shingles Prevention Study subpopulation followed for 7 years post-vaccination. Zoster vaccine was generally well tolerated in older adults. In older adults, the zoster vaccine has the potential to significantly reduce the herpes zoster burden of illness by decreasing the incidence of herpes zoster or reducing its severity(17).

5. Avoid contact to people with chickenpox
If you have not had chickenpox before, exposed yourself to people who have chickenpox can cause increased risk of Shingles.

6. Eat your fruits and vegetable
Fruits and vegetables contain high amount of nutrients and antionxidants of which can increase the function of immune system in fighting not only the forming of free radicals but also viral and bacterial causes of infection and inflammation.

7. Moderate exercise
Extreme exercise can weaken the immune system, but  moderate exercise enhance them. Clinical data support the concept that heavy exertion increases the athlete's risk of URTI because of negative changes in immune function and elevation of the stress hormones, epinephrine, and cortisol. On the other hand, there is growing evidence that moderate amounts of exercise may decrease one's risk of URTI through favorable changes in immune function without the negative attending effects of the stress hormones(18).

8. Relaxation
Stress is often associated with an increased occurrence of autonomic, cardiovascular, and immune system pathology. Dr. Gopal A, and the team at the Lady Hardinge Medical College in the study of sixty first-year MBBS students randomly assigned to yoga group and control group (30 each). The yoga group underwent integrated yoga practices for 35 minutes daily in the presence of trained yoga teacher for 12 weeks. Control group did not undergo any kind of yoga practice or stress management, showed that Yoga resists the autonomic changes and impairment of cellular immunity seen in examination stress(19)

9. Etc.

B. Diet against shingles
The aims of the diet against shingle is to enhace the immune system by taking fruits and vegatables which contains high amount of antioxidant to fight off the viral causes of infections
1. Wolfberry is the common name for the fruit of two very closely related species, the genus of Lycium, belong to family Solanaceae, native to native to southeastern Europe and Asia.
a.  Anticancer and immunomodulatory effects
In the classification of the anticancer effects of traditional Chinese medicine (TCM) used in cancer therapies found that major active ingredients, L. barbarum polysaccharides (LBP), scopoletin and 2-O-β-D: -glucopyranosyl-L: -ascorbic acid (AA-2βG), are found to have apoptotic and antiproliferative effects on cancer cell lines. Moreover, LBP also contributes to body's immunomodulatory effects and enhances effects of other cancer therapies. It is not known whether there are any undesirable effects, according to "A review of the anticancer and immunomodulatory effects of Lycium barbarum fruit" by Tang WM, Chan E, Kwok CY, Lee YK, Wu JH, Wan CW, Chan RY, Yu PH, Chan SW.(20)

b. Hypochlolesterolemic and antioxidative effects
In the researches of the hypocholesterolemic effect and potential of tyramine derivatives from Lycii Cortex Radicis (LCR), the root bark of lycium (Lycium chenese Miller) in reducing lipid peroxidation found that The level of liver cholesterol was significantly lower in LCR1 and LCR2 groups than HF-control. Serum levels of TBARS were significantly lower only in LCR2 group when compared with HF-control group. From the observed results, we concluded that LCR can be utilized as a hypocholesterolemic ingredient in combination with ginger, especially for functional foods, according to "Study on the hypochlolesterolemic and antioxidative effects of tyramine derivatives from the root bark of Lycium chenese Miller" by Cho SH, Park EJ, Kim EO, Choi SW.(21)

2. Oranges
Orange is a species of Citrus Sinensis, belong to the family Rutaceae and native to the Southeast Asia. Orange is round citrus fruits with finely-textured skins, orange in color and one of most popular fruits in the world.
a. Bioavailability and antioxidant effects
In the reserach of Bioavailability and antioxidant effects of orange juice (OJ) into habitual diet found that after the 3 week intervention, plasma concentrations of vitamins A and E did not change. 8-Hydroxydeoxyguanosine in white blood cells declined by 16% (p = 0.38; n = 11), and in individuals with high baseline concentrations by 29% (p = 0.36; n = 7), respectively. Low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol ratios decreased but cholesterol (HDL, LDL, total) and thiobarbituric acid reactive substance plasma concentrations did not change significantly, according to "Bioavailability and antioxidant effects of orange juice components in humans?" by Franke AA, Cooney RV, Henning SM, Custer LJ.(22)

b.  Vitamin C
a. Capillaries
Since it contains high amount of vitamin C, it reduces the risk of breaking off of the small vessels, thus preventing the risk of infection, inflammation, according to the study of "High-dose vitamin C treatment reduces capillary leakage after burn plasma transfer in rats" by Kremer T, Harenberg P, Hernekamp F, Riedel K, Gebhardt MM, Germann G, Heitmann C, Walther A.(23)

b. Immune system
Vitamin C is considered as on of most powerful free radical scavenger, it helps to enhane the immune system fighting against forming of free radical cause of irregular cells growth due to mutation of cells' DNA, including tumors and cancers, according to the study of "Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later?" by Cabanillas F.(24)

2. Pomegranates is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.
a.  Antiproliferative, apoptotic and antioxidant activities
In the assessment of polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid (EA) of Pomegranate (Punica granatum L.) fruits juice (PJ) and its antioxidant and anti-atherosclerotic activities found that Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 microg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients, according to "In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice" by Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D.(25)

b. CatechinsCatechin, a polyphenol found abundantly in Pomegranates has exerted its antioxidant effect in reducing the risk of forming of free radicals, according to "Catechins and procyanidins in berries of vaccinium species and their antioxidant activity" by Määttä-Riihinen KR, Kähkönen MP, Törrönen AR, Heinonen IM.(26)

5.  Blueberry is a flower plant, belong to the family Eriaceae and native to Northern America. It can grows from 10 cm to 4 meters tall.
In the investigation of Blueberry and blackberry wines commercially available in Illinois and theirs potential health benefits, found that fruit wines made from blueberries and blackberries may have potential health applications and therefore could contribute to the economy of the wine industry. Practical Application: The majority of wines are produced from grapes, but wine can also be produced from other fruits including blueberries and blackberries, which contain phenolic compounds that may contribute to human health, according to "Comparison of Chemical Composition and Antioxidant Capacity of Commercially Available Blueberry and Blackberry Wines in Illinois" by Johnson MH, Gonzalez de Mejia E.(27)

6. Coriander is an annual herb, genus Coriandrum in the family Apiaceae, native to southern Europe and North Africa to southwestern Asia. All parts of the plant are edible, but the fresh leaves and the dried seeds are the parts most commonly used in cooking.
a. Anti-anxiety activity
In the evaluation of anti-anxiety activity of hydroalcoholic extract of Coriandrum sativum (Linn.) found that extract of C. sativum at 100 and 200 mg/kg dose produced anti-anxiety effects almost similar to diazepam, and at 50 mg/kg dose did not produce anti-anxiety activity on any of the paradigm used, according to "Anti-anxiety activity of Coriandrum sativum assessed using different experimental anxiety models" by Mahendra P, Bisht S.(28)

b. Antioxidant and hepatoprotective effect
In the investigation of essential oils of Coriandrum sativum L. and Carum carvi L. fruits and their antioxidant activity and hepatoprotective effect against carbon tetrachloride (CCl(4)) damage found that coriander essential oil exhibited prooxidant activity, according to "Antioxidant and hepatoprotective potential of essential oils of coriander (Coriandrum sativum L.) and caraway (Carum carvi L.) (Apiaceae)" by Samojlik I, Lakić N, Mimica-Dukić N, Daković-Svajcer K, Bozin B.(29)

7. Etc

There is no specific fruits or vegetables for preventing shingle, please consult the world most healthy foods for more enhanced immune system foods(30).
  
C. Antioxidants against shingles
C.1. Antioxidant enzymes
1. Glutathione reductase
Glutathione reductase, an enzyme reduces pair of sulfur atoms glutathione to the a organosulfur compound form of antioxidant (consisting of three amino acids joined by peptide bonds) which helps to prevent damage of important cellular components caused by free radicals and peroxides.

2. Super oxide dismutase (both Cu-Zn and Mn)
Super oxide dismutase is an important antioxidant defense in nearly all cells exposed to oxygen by converting superoxide into oxygen and hydrogen peroxide depending on the metal cofactor such as both Cu-Zn and Mn.

3. Etc.

C.2. Metals binding proteins
1. Lactoferrin
Lactoferrin, a multifunctional protein of the transferrin family, is one of the components of the immune system of the body by fighting against foreign invasion of bacteria and virus and lipid oxidation by inhibiting oxidation in a concentration-dependent manner even at concentrations beyond its capacity.

2. Metallotheinein
Metallotheinein, a family of cysteine-rich, low molecular weight proteins helps to bind both physiological heavy metals through the organosulfur compound of its cysteine residues. It also captures harmful superoxide and hydroxyl radicals by liberating the metal ions which were bound to cysteine.

3. Etc.

C.3. Common Free Radical Scavengers
1. Bilirubin
Bilirubin is a prosthetic group which helps to break down molecules into smaller units in releasing energy, excreted in bile and urine. It is a cellular antioxidant, by reverting to biliverdin, a green tetrapyrrolic bile pigment, once again when oxidized that inhibits the effects of mutagens.

2. Carotenoids
Carotenoids are organic pigments, occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria.
a. Beta-carotene
Beta-Carotene, an organic compound and classified as a terpenoid, a strongly-coloured red-orange pigment in plants and fruits.
a.1. It is not toxic and stored in liver for the production of vitamin A that inhibits cancer cell in experiment. Beta-carotene also neutralize singlet oxygen before giving rise of free radicals which can damage of DNA, leading to improper cell DNA replication, causing cancers.
a.2. Cell communication
Researcher found that beta-carotene enhances the communication between cell can reduce the risk of cancer by making cells division more reliable.
a.3. Immune system
Beta-carotene promotes the immune system in identifying the foreign invasion such as virus and bacteria by increasing the quality of MHC2 protein in maintaining optimal function of white cells.
a.4. Polyunsaturated fat
Researchers found that beta-carotene also inhibits the oxidation of polyunsaturated fat and lipoprotein in the blood that reduce the risk of plaques build up onto the arterial walls, causing heart diseases and stroke.
a.5. There are more benefits of beta-carotene.

b. Alpha-carotene
Alpha-carotene, one of the most abundant carotenoids in the North American diet, is a form of carotene with a β-ring at one end and an ε-ring at the other. It is the second most common form of carotene which not only protects cells from the damaging effects of free radicals and enhances the immune system in fighting against bacteria and virus invasion, but also stimulates the communication between cells thus preventing irregular cell growth cause of cancers.

c. Beta-cryptoxanthin
Beta cryptoxanthin is an antioxidant, beside helping to prevent free radical damage to cells and DNA but also stimulates the repair of oxidative damage to DNA. it enhances the immune function infighting against inflammatory cause of polyarthritis, and irregular cell growth cause of cancer due to oxidation.

d. Lutein
Lutein is one of the most popular North American carotenoids. It is found in greens like kale and spinach as well as the yolk of eggs. Lutein is also found in the human eye. Getting enough lutein in your diet may help to fight off age related macular degeneration, an eye condition.
Researcher has shown that people who do not have enough lutein in their diet will not have enough lutein present in the muscular part of the eye. This is what likely leads to age related macular degeneration that can result in blindness.


3. Etc.


C.4. Other antixidants
1. Selenium
Selenium , a trace mineral plays an important and indirect role as an antioxidant by fulfilling its function as a necessary constituent of glutathione peroxidase and in production of glutathione, that inhibits the damage caused by oxidation of free radical hydrogen peroxide, leading to aging effects.

1.1. Heart health
Since it works synergism with vitamin E, it promotes heart health. Study showed by increasing the levels of glutathion, selenium decreases the risk of LDL oxidation, thus lowering the risk of plaque building up on the arterial walls, blood pressure and heart diseases.
1.2. Immune system
Selenium enhances the immune function that fighting off the attack of AID virus by promoting the function of interleukin 2 and T-cells.

1.3. Cancer
Study showed that levels pf selenium in blood test is associated with high rate of cancer, including skin cancer.

2. Zinc
Zinc is an essential mineral that is naturally present in some foods. The ability of zinc in inhibiting oxidative processes has been recognized for many years. Chronic effects, zinc enhances the introduction of metallothioneins, which help to capture the superoxide and hydroxyl radicals due to cysteine residues, resulting in lessening the risk of oxidative stress.
Over acute effects, zinc may reduce the postischemic injury to a variety of tissues and organs by involving the antagonism of copper reactivity as a result from its antioxidant functions.



C.5. Etc.
There are more antioxidants which can help to enhance the immune function(31)


D. Phytochemicals against shingles
D.1. Quercetin is a member of flavonoids, found in fruits, vegetables, leaves and grains. It is also one of antioxidants with property of protecting our body in fighting against forming of free radicals cause of mutation of cells`DNA.
a. Anti-Inflammatory
According to the study of `Antioxidant and Anti-Inflammatory Activities of Quercetin 7-O-β-D-Glucopyranoside from the Leaves of Brasenia schreberi.`by Legault J, Perron T, Mshvildadze V, Girard-Lalancette K, Perron S, Laprise C, Sirois P, Pichette A. (Source from Laboratory for Analysis and Separation of Plant Species (LASEVE), Université du Québec à Chicoutimi , Chicoutimi, Québec, Canada.), posted in PubMed, researchers found that some flavonoids have been reported to possess beneficial effects in cardiovascular and chronic inflammatory diseases associated with overproduction of nitric oxide. Quercetin-7-O-β-D-glucopyranoside possesses anti-inflammatory activity, inhibiting expression of inducible nitric oxide synthase and release of nitric oxide by lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. Quercetin-7-O-β-D-glucopyranoside also inhibited overexpression of cyclooxygenase-2 and granulocyte macrophage-colony-stimulating factor.

b. Antimicrobial and cytotoxic activities
According to the study of `Antimicrobial and cytotoxic activities of leaves, twigs and stem bark of Scutia buxifolia Reissek.`by Boligon AA, Janovik V, Frohlich JK, Spader TB, Forbrig Froeder AL, Alves SH, Athayde ML. (Source from a Phytochemical Research Laboratory, Department of Industrial Pharmacy , Federal University of Santa Maria , Build 26, room 1115 , Santa Maria , CEP 97105-900 , Brazil.), posted in PubMed, researchers found that quercitrin, isoquercitrin and rutin were identified by HPLC and may be partially responsible for the antimicrobial activities observed. This study reports for the first time the antimicrobial and cytotoxic activities of S. buxifolia leaves, twigs and stem bark.

D.2. Naringenin, a flavanone, belonging to the red, blue, purple pigments of Flavonoids (polyphenols) found predominantly in citrus fruits is considered as one of powerful antioxiant with many health benefits.
1. Antioxidant, radical scavenging and biomolecule activity
In the affirmation of the capacity of flavonoid naringenin and its glycoside naringin in the comparison of theirs antioxidant capacities, radical scavenging and biomolecule activities found that naringenin exhibited higher antioxidant capacity and hydroxyl and superoxide radical scavenger efficiency than naringin and both flavanones were equally effective in reducing DNA damage. However, they show no protective effect on oxidation of GSH, according to the study of "Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study" by Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez-Mateos M, Muñiz P.(32) 

2. Anti-inflammatory effects
In the evaluation of the mechanisms of action of the effective compounds. Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin amd theirs anti-inflammatory effects found that they inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner, according to "Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages" by Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E.(33)

3. Immunity
In the unvestigation of Naringenin, a flavonoid in grapefruits and citrus fruits and its effec in immune system found that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment, according to "A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression" by Fang F, Tang Y, Gao Z, Xu Q.(34) 

D.3. Tangeritin, one of the flavones, is found in tangerine and many citrus peels 
1. Antioxidants
In the comparison of hand-pressed juice of polymethoxylated flavones (PMFs) and flavanone glycosides (FGs) and the peeled fruit of 'Sainampueng' tangerines ( Citrus reticulata Blanco cv. Sainampueng) antioxidant effects found that hand-pressed juice of C. reticulata Blanco cv. Sainampueng serves as a rich source of PMFs, FGs, carotenoids, and antioxidants: 4-5 tangerine fruits ( approximately 80 g of each fruit) giving one glass of 200 mL hand-pressed juice would provide more than 5 mg of nobiletin and tangeretin and 36 mg of hesperidin, narirutin, and didymin, as well as 30 mg of ascorbic acid, >1 mg of provitamin A active beta-cryptoxanthin, and 200 microg of alpha-tocopherol, according to "Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines ( Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand" by Stuetz W, Prapamontol T, Hongsibsong S, Biesalski HK.(35)

2. Antimicrobial activity
In the study of antibacterial and antifungal properties of wax and hexane extracts of Citrus spp. peels found that antimicrobial activity especially against M. canis and T. mentagrophytes: 4',5,6,7,8-pentamethoxyflavone (tangeritin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) from C. reticulata; and 6,7-dimethoxycoumarin (also known as escoparone, scoparone or scoparin) from C. limon, according to "Antimicrobial activity of wax and hexane extracts from Citrus spp. peels" by Johann S, Oliveira VL, Pizzolatti MG, Schripsema J, Braz-Filho R, Branco A, Smânia Jr A.(36)

D.4. Gallocatechin, containing catechin is phytochemicals of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in green tea, almonds, black diamond plums, black tea, cocoa beans, Fuji apples, golden delicious apple, etc.
a. Antioxidant and anti-inflammatory activities
In the evaluation of the radioprotective efficacy of green tea polyphenols and the component ingredients against irradiated-induced damage in mice and elucidate the underlying mechanisms, found that Moreover GTP and its bioactive components (catechin, epigallocatechin and epigallocatechin-3-gallate) assisted in decreasing the leukocytopenia seen after whole mice irradiation and significantly reduced the elevated serum inflammatory cytokines (TNF-α, IL-1β, and IL-6). Green tea polyphenols have a potential to be developed as radioprotective agents against irradiated-induced toxicity. Furthermore the antioxidant and anti-inflammatory activities of GTP can be attributed to the interaction of the different components through multiple and synergistic mechanisms, according to "Bioactive components from the tea polyphenols influence on endogenous antioxidant defense system and modulate inflammatory cytokines after total-body irradiation in mice" by Hu Y, Guo DH, Liu P, Cao JJ, Wang YP, Yin J, Zhu Y, Rahman K.(37)

b. Anti-inflammatory and antimicrobial effects
In the evaluation of the anti-inflammatory and antimicrobial effect of nanocatechin on CBP and plasma concentration of catechins in an animal model, found that the use of ciprofloxacin, catechin, and nanocatechin showed statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the control group. The nanocatechin group showed statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the catechin group. Plasma concentrations of epicatechin, gallocatechin gallate, and epigallocatechin gallate were significantly higher in the nanocatechin group than those in the catechin group. These results suggest that nanocatechin has better antimicrobial and anti-inflammatory effects on rat CBP than catechin due to higher absorption into the body, according to "Anti-inflammatory and antimicrobial effects of nanocatechin in a chronic bacterial prostatitis rat model" by Yoon BI, Ha US, Sohn DW, Lee SJ, Kim HW, Han CH, Lee CB, Cho YH.(38)

D.5. Gallic acid is a phytochemical in the class of Phenolic acids, found abundantly in tea, mango, strawberries, rhubarb, soy, etc.
a. Cytotoxic and antioxidative activities
In the investigation of the bioactivity guided isolation and characterization of phytoconstituents, indicated the extract showed strong radical scavenging effects against DPPH, nitric oxide (NO) and superoxide (SO) radicals comparable to that of known antioxidants 3-t-butyl-4-hydroxyanisole, ascorbic acid (vitamin C), and quercetin in addition to its cytotoxic activities against HEP-2 (human larynx epidermoid carcinoma) and RD (human rhabdomyosarcoma) cell lines based on MTT assay for growth inhibition. The gallic acid equivalent total phenolic content of the plant was found to be 79.94mg/g dry extract. Phenylethanoid glycosides, verbascoside and calceorioside A were isolated from the most active fraction and both compounds showed strong radical scavenging activity against tested radicals and cytotoxicity against HEP-2, RD and MCF-7 (human breast adenocarcinoma) cell line, according to "Cytotoxic and antioxidative activities of Plantago lagopus L. and characterization of its bioactive compounds" by Sebnem Harput U, Genc Y, Saracoglu I.(39)

b. Antioxidants
In the evaluation of the antioxidant, anti-inflammatory, and antiproliferative activities of organic fractions from Cystoseira sedoides (Desfontaines) C. Agardh, indicated that the F-CHCl(3) and F-AcOEt fractions showed significant total phenolic content at 55.09 and 61.30 mg gallic-acid equivalent/g dried sample, respectively. Using the DPPH method, the F-CHCl(3) and the F-AcOEt fractions exhibited the strongest radical scavenging activity, with IC(50) 120 µg/mL for F-CHCl(3) and 121 µg/mL for F-AcOEt, which approaches the activity of the powerful antioxidant standard, Trolox (IC(50) = 90 µg/mL), according to "Antioxidant, anti-inflammatory, and antiproliferative activities of organic fractions from the Mediterranean brown seaweed Cystoseira sedoides" by Mhadhebi L, Laroche-Clary A, Robert J, Bouraoui A.(40)

D.6. Lycotene is a phytochemical compound and bright red pigment belonging to group of carotene in the family of carotenoids found mostly in tomatoes and other red fruits and vegetables. It best known for its inverse correlation between consumption of tomatoes and cancer risk. It has been studied by many researches as a potential compound for prevention and treatment for certain cancers, including prostate and liver cancer.
a. Inflammation
According to the study of `Inhibitory mechanism of lycopene on cytokine expression in experimental pancreatitis.`by Kim H. (Source from Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, South Korea. kim626@yonsei.ac.kr), posted in PubMed, researchers found that in pancreatic acinar cells, which is mediated by the activation of NADPH oxidase. Lycopene functions as a very potent antioxidant to suppress the induction of inflammatory cytokines, in pancreatic acinar cells stimulated with cerulein. In this review, the possible beneficial effect of lycopene on experimental pancreatitis shall be discussed based on its antioxidant activity.

b. Antioxidants
In the study of `Comparison of lycopene and tomato effects on biomarkers of oxidative stress in vitamin E deficient rats` by Delphine Gitenay, Bernard Lyan, Mathieu Rambeau, Andrzej Mazur and Edmond Rock. (Source from European Journal of Nutrition Volume 46, Number 8, 468-475, DOI: 10.1007/s00394-007-0687-2), posted in springerprotocols.com, researchers found that Our study showed for the first time that tomatoes, containing or not containing lycopene, have a higher potential than lycopene to attenuate and or to reverse oxidative stress-related parameters in a mild oxidative stress context.

D.7. Etc.
 
E. Etc.

VI. Treatments
A. In the conventional medicine perspective
1. Topical cream
Some researchers suggest that the lidocaine plaster could be at least as effective as systemic pregabalin in the treatment of postherpetic neuralgia and painful diabetic polyneuropathy. Open-label studies indicate efficacy in the treatment of other localized neuropathic pain conditions, such as painful idiopathic sensory polyneuropathy, complex regional pain syndrome, carpal tunnel syndrome sequelae, postsurgical and posttraumatic pain. Quality of life markedly improved in a variety of neuropathic pain conditions and long-term treatment provided sustained relief in patients with neuropathic pain who are responsive to lidocaine plaster. The lidocaine plaster is usually well tolerated. The risk of systemic adverse events and pharmacokinetic interactions with concomitant medication is minimal owing to low systemic exposure(d)

2. Other medication
Dr. Kofoed K. and the team of researchers at the Dermato-venerologisk Afdeling D41, Bispebjerg Hospital, showed that Post-herpetic neuralgia (PHN) is persistent pain three months after the rash started. In recent years several Cochrane reviews and clinical studies on how to treat HZ and PHN have been published. These studies show that early recognition and treatment can reduce acute symptoms, that antiviral therapy and corticosteroids shorten the acute illness period, that opioids and anticonvulsants have effect on acute HZ pain and, finally, that tricyclic antidepressants, opioids and anticonvulsants all have proven efficiency in PHN therapy.(e)

3. Etc.

B. In herbal medicine perspective
The aims of herbal treatment is to enhace the self defense of the immune system
B.1.  Alfalfa is a flowering plant in the genus Medicago, belonging to the family Fabaceae, It has been cultivated all over the world as hay for cattle feeding. The leaves, sprouts, and seeds to make medicine has been used in traditional medicine over 15010 years to treat high cholesterol, asthma, osteoarthritis, rheumatoid arthritis, diabetes, enhance digestive system, bleeding disorder, kidney and urinary tract infection, etc. North Americal aboriginal has used Alfalfa seed as food, such as making bread and mush.
1. Antioxidant
In a study of measurements of pH, water holding capacity, color, oxymyoglobin content, TBARS and oxidation-reduction potential in evaluating the effects of a dietary protein-xanthophylls (PX) concentrate of alfalfa to turkey diets conducted by University of Life Sciences in Lublin, Skromna 8, 20-704 Lublin, Poland.(a), researchers found that TBARS and oxidation-reduction potential values suggested that the inclusion of the concentrate to turkey diets acts as an antioxidant in the raw meat.

2. Disease of autoimmune
In a study of five groups of 12-week-old female mice were per oral treated with vehicle (control), lyophilized AS (550 mg wt/kg BW), ASEA (ASEA, 25 mg/kg BW), coumestrol (CUM, 0.075 mg/kg BW) and tamoxifen (TAM, 0.375 mg/kg BW) as the positive control, conducted by Institute of Microbiology and Biochemistry, College of Life Science, National Taiwan University, Taipei, Taiwan (b), researchers found that alhalfa decreased the disease severity, increased survival and life span of the autoimmune-prone MRL-lpr/lpr mice, suggesting a potential of ASEA in the treatment of autoimmune diseases.

3. Anti-inflammatory activity
In a study of anti-inflammatory effects may be used for inflammatory disorders by examining alfalfa sprout ethyl acetate extract (ASEA) in ,ice coducted by College of Life Science, National Taiwan University, Taipei, Taiwan, Republic of China.(c), researchers found that significantly higher survival rates than the control group and suggests that ASEA supplementation can suppress the production of pro-inflammatory cytokines and alleviate acute inflammatory hazards.

B.2. Black Cohosh is a herbaceous perennial plant, genus Actaea, belonging to the family Ranunculaceae, native to eastern North America. The herb has been used in traditional medicine as analgesic, sedative, diuretic, emmenagogue anti-inflammatory agent and to treat rheumatism, symptoms of menopause, uterine cramps and muscle pain, etc.. Native Americans have used the root of the herb to treat snake bite.
a. Antioxidants
Polyphenols in Black cohosh may be considered as an antioxidant which help to fight against the forming of free radicals cause of DNA damage and guarding our body against foreign invasion such as bacteria and virus, according to the study of "Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: bioassay-directed isolation and characterization of active principles" by Burdette JE, Chen SN, Lu ZZ, Xu H, White BE, Fabricant DS, Liu J, Fong HH, Farnsworth NR, Constantinou AI, Van Breemen RB, Pezzuto JM, Bolton JL., posted in PubMed(41)

b.2. Anti-inflammation
Cimicifuga racemosa (Actaea racemosa, black cohosh)have exerted inflammatory activity by inhibiting nitric oxide production by reducing iNOS expression without affecting activity of the enzyme, according to the study of "Inhibition of inducible nitric oxide synthesis by Cimicifuga racemosa (Actaea racemosa, black cohosh) extracts in LPS-stimulated RAW 264.7 macrophages" by Schmid D, Gruber M, Woehs F, Prinz S, Etzlstorfer B, Prucker C, Fuzzati N, Kopp B, Moeslinger T., posted in PubMed(42)

B.3. 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.
a. Anxiety
Matricaria recutita (chamomile) extract therapy has exerted the modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder, according to the study of "A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder" by Amsterdam JD, Li Y, Soeller I, Rockwell K, Mao JJ, Shults J.(43)

b. Anti-inflammatory effects
Chamomile has demonstrated the inhibition of NO production and iNOS gene expression by inhibiting RelA/p65 activation and supports the utilization of chamomile as an effective anti-inflammatory agent, according to the study of "Chamomile: an anti-inflammatory agent inhibits inducible nitric oxide synthase expression by blocking RelA/p65 activity' by Bhaskaran N, Shukla S, Srivastava JK, Gupta S.(44)

c. Immunomodulatory effect
Extracts of Silene (Silene nocturna), Black seed (Nigella sativa) and Chamomile (Matricaria chamomilla) have exerted significantly (P < 0.01) restored their resistance against lethal infection with the predominately granulocyte-dependant Candida albicans, according to the study of "Evaluation of immunomodulatory effect of three herbal plants growing in Egypt" by Ghonime M, Eldomany R, Abdelaziz A, Soliman H.(45)

B.4. Grapefruit seed extract (GSE) is a liquid extracted from the seeds, pulp, and white membranes of grapefruit. The herb has been used in traditional medicine as an anti bacterial, viral, fungal, parasites and to enhance immune system, protect against colds and flu and malignant disease.
a. Antimicrobial activity
In the determination of antibacterial and antifungal activity of ethanolic extract of grapefruit (Citrus paradisi Macf., Rutaceae) seed and pulp found that ethanolic extract exibited the strongest antimicrobial effect against Salmonella enteritidis (MIC 2.06%, m/V). Other tested bacteria and yeasts were sensitive to extract concentrations ranging from 4.13% to 16.50% (m/V), according to "Antimicrobial activity of grapefruit seed and pulp ethanolic extract" by Cvetnić Z, Vladimir-Knezević S.(46)

b. Antioxidant activity
In analyzing the antioxidant activity of Citrus paradisi (grapefruit) seeds glyceric extract dissolved in ethanol and in aqueous media found that grapefruit seeds glyceric extract utilized as aqueous solutions demonstrated antioxidant properties better than those displayed by alcoholic solutions. according to "Antioxidant activity of Citrus paradisi seeds glyceric extract" by Giamperi L, Fraternale D, Bucchini A, Ricci D.(47)

B.5.  Shiitake mushroom is an edible mushroom, genus Lentinula, belonging to family Marasmiaceae, native to East Asia and widely cultivated for consumption for its health benefits and commercial purpose in many Asian countries. The herb has been used in traditional medicine as blood tonic agent and to strengthen immune system, treat colds, measles, bronchial inflammations, etc.
a. Immune system
Shiitake mushroom enhances the immune system in fighting against infection and disease. influenza, viruses and irregular cells growth due to it anti-tumor polysaccharide lentinan, according to "Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers" by Yoshino S, Tabata T, Hazama S, Iizuka N, Yamamoto K, Hirayama M, Tangoku A, Oka M.(48)

b. Cholesterol
It also enhances the ration levels of blood cholesterol due to its active compound eritadenine, according to "Eritadenine-induced alterations of plasma lipoprotein lipid concentrations and phosphatidylcholine molecular species profile in rats fed cholesterol-free and cholesterol-enriched diets" by Shimada Y, Morita T, Sugiyama K.(49)

c. Free radicals
Shiitake mushroom contains high levels of antioxidants such as L-ergothioneine, that helps to
reduce the risk of oxidative cause of mutation in cell division and alternation, according to"Ergothioneine; antioxidant potential, physiological function and role in disease" by Cheah IK, Halliwell B.(50)

d. Liver diseases
Extracts of the mycelium of shiitake mushrooms not only protect the liver but also recover from liver fibrosis, according to "Effects and mechanisms of Acremoniumterricola milleretal mycelium on liver fibrosis induced by carbon tetrachloride in rats" by Tian XP, Yin YY, Li X.(51)

B.6. Ginseng Asia is also known as Panax ginseng. Since it has been grown in the cold places in the Asian, Asian ginseng is considered as yang promoting, according to traditional Chinese medicine.
The herb has been used in traditional and Chinese medicine to promote yang and to improve cardiac function, short of breath, blood pressure. Panax ginseng can generates fluids and reduce thirst, to treat anxiety, insomnia, dizziness/headache, forgetfulness, impotence, diabetes, bleeding in the vagina not during period, etc.
a. Antioxidant activity
In the evaluation of the extraction conditions of polysaccharides from the rhizomes of Panax japonicus C.A. Meyer and its antioxidant effect found that antioxidant activity exhibited Panax japonicus polysaccharides (PJP) had a good potential for antioxidant, according to "Optimization of polysaccharides from Panax japonicus C.A. Meyer by RSM and its anti-oxidant activity" by Wang R, Chen P, Jia F, Tang J, Ma F.(52)

b.  Immunological activities
In the study of Water-soluble ginseng oligosaccharides (designated as WGOS) with a degree of polymerization ranging from 2 to 10 were obtained from warm-water extract of Panax ginseng roots, found that WGOS were potent B and T-cell stimulators and WGOS-1 has the highest immunostimulating effect on lymphocyte proliferation among those purified fractions. It is hoped that the WGOS will be developed into functional food or medicine, according to "Structural characterization and immunological activities of the water-soluble oligosaccharides isolated from the Panax ginseng roots" by Wan D, Jiao L, Yang H, Liu S.(53)

B.7. For more infoprmation of other herbs and singles, please visit(54)

C. In Traditional Chinese perspective (55)
C.1. Herbal treatment
Depending to the differentiation, some traditional Chinese medicine practitioner define shingles as  a result of Stagnated Heat in the Liver meridian bright red with distended pain, Damp/Heat in Spleen meridian and Chronic Blood Stasis
C.1. 1. Stagnated Heat in the Liver meridian bright red with distended pain with treatments of Herbal Formula: Huang Lian Jie Du Tang + Xi Jiao Di Huang Tang
1. Huang Lian Jie Du Tang (clear heat and damp-heat in all three burners), ingredients include
a. Huang Lian (coptis, Coptidis Rhizoma), 9g
b. Huang Qin (scutellaria, Scutellariae Radix) 6g
c.  Huang Bai (phellodendron, Phellodendri Cortex) 6g
d. Zhi Zi (gardenia, Gardeniae Fructus) 9 g

2.  Xi Jiao Di Huang Tang (clears Heat/Fire toxin, cools blood, nourish Yin, moves Blood Stasis, stops bleeding)
a. Xi Jiao (cornu rhinoceri) 3g
b. Sheng Di Huang (radix rehmanniae glutinosae) 24g
c. Shao Yao (radix paeoniae) 9g
d. Mu Dan Pi (cortex moutan radicis) 6g
 
C.1.2. Damp/Heat in Spleen meridian with Herbal Formula Chu Shi Wei Ling Tang
1. Functions
Eliminate Dampness by Combining Calm the Stomach and Five
2. Ingredients
a Fang Feng (saposhnikovia root) 3g
b.  Zhi Zi (cape jasmine fruit)  3g
c. Zhu Ling (polyporus) 3g
d. Hua Shi  (talcum) 3g
e. Mu Tong  (akebia caulis) 3g
f. Deng Xin Cao (juncus pith 3g
g. Ze Xie (water plantain) 3g
h. Hou Po (magnolia bar 3g
i. Cang Zhu (atractylodes rhizome) 3g
j. Chen Pi (tangerine peel) 3g
k. Decoction Rou Gui (cinnamon bark) 0.9g

C.1. 3. Chronic Blood Stasis (Last stage of shingles)with Herbal Formula Tao Hong Si Wu Tang
1. functions
Blood deficiency with mild Blood stagnation in the lower jiao, Tonifies and regulates qi and blood, gently moves stagnant blood and warms the uterus.
2. Ingredients
a. Chuan Xiong (Sichuan lovage root) 3g
b. Tao Ren (peach kernel) 6g
c. Hong Hua (safflower flower) 3g
d. Shu Di Huang (cooked rehmannia root) 6g
e. Dang Gui (Chinese angelica root) 6g
f. Bai Shao  (white peony root) 6g

C.2. Cupping theory
Traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world, Dr. Cao H, and the research team at University of Western Sydney indicated that numerous RCTs on cupping therapy have been conducted and published during the past decades showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted.(56).
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hyperlipoproteinemia", posted in PubMed
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(c) "Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit lipopolysaccharide-induced inflam
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