Chyawanprash: A review of therapeutic benefits as in authoritative texts and documented clinical literature.

ETHNOPHARMACOLOGICAL RELEVANCE: Chyawanprash (CP), a traditional immune booster recipe, has a long history of ethnic origin, development, household preparation and usage. There are even mythological stories about the origin of this recipe including its nomenclature. In the last six decades, CP, because of entrepreneurial actions of some research Vaidyas (traditional doctors) has grown to industrial production and marketing in packed forms to a large number of consumers/patients like any food or health care product. Currently, CP has acquired a large accepted user base in India and in a few countries out-side India. AIM OF THE STUDY: Authoritative texts, recognized by the Drugs and Cosmetics Act of India, describe CP as an immunity enhancer and strength giver meant for improving lung functions in diseases with compromised immunity. This review focuses on published clinical efficacy and safety studies of CP for correlation with health benefits as documented in the authoritative texts, and also briefs on its recipes and processes. MATERIALS AND METHODS: Authoritative texts were searched for recipes, processes, and other technical details of CP. Labels of marketing CP products (Indian) were studied for the health claims. Electronic search for studies of CP on efficacy and safety data were performed in PubMed/MEDLINE and DHARA (Digital Helpline for Ayurveda Research Articles), and Ayurvedic books were also searched for clinical studies. RESULTS: The documented clinical studies from electronic databases and Ayurvedic books evidenced that individuals who consume CP regularly for a definite period of time showed improvement in overall health status and immunity. However, most of the clinical studies in this review are of smaller sample size and short duration. Further, limitation to access and review significant data on traditional products like CP in electronic databases was noted. CONCLUSIONS: Randomized controlled trials of high quality with larger sample size and longer follow-up are needed to have significant evidence on the clinical use of CP as immunity booster. Additional studies involving measurement of current biomarkers of immunity pre- and post-consumption of the product as well as benefits accruing with the use of CP as an adjuvant are suggested.

Comparative Evaluation of Specific Phytochemical Indicatives in Cirivilvadi Kasaya Prepared Freshly and at Commercial Scale.

Kasaya or decoction is an Ayurvedic dosage form, prescribed based on the stage of the disease according to the principles of Ayurveda. This dosage form is traditionally prepared fresh and consumed on the same day but for the sake of convenience; the process of preparation has been modified so that it can be stored with longer shelf life, easy availability and produced in large quantities. There is a need to understand the implications of this modification in terms of chemical changes. This work attempted to check the phytochemical profile of both freshly prepared decoction and commercially available decoction with reference to some analytical parameters like pH, total soluble solids, phenols, alkaloids, potassium and to assess the changes in the thin layer chromatography profiling of the decoction. The results showed that phenols and potassium are found to be two fold higher in freshly prepared decoction, compared to commercially available decoction diluted to dosage in practice (1:4 ratio). However, the total alkaloid content was found to be approximately ten fold higher in commercially available decoction. It was observed that the thin layer chromatography profile of decoctions was extracted into petroleum ether and chloroform was similar and consistent with different batches though the bands in commercially available decoction were slightly more intense compared to freshly prepared decoction. The total soluble solids in commercially available decoction were four times higher than freshly prepared decoction. The study reveals that there are differences in the phytochemical profiles of the freshly prepared decoction and commercially available decoction of the same formulation. However, the significance of these differences can be determined only by further clinical studies. On the other hand, the study lends support to the practice of diluting the commercially available decoction to make it equivalent to freshly prepared decoction.

Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer cell lines.

In an effort to establish new candidates with enhanced anticancer activity of 5-hydroxy-7-methyl-1,4-naphthoquinone scaffold (7-methyljuglone) previously isolated from the root extract of Euclea natalensis, a series of 7-methyljuglone derivatives have been synthesized and assessed for cytotoxicity on selected human cancer lines. These compounds were screened in vitro for anticancer activity on MCF-7, HeLa, SNO and DU145 human cancer cell lines by MTT assay. Most of them exhibited significant toxicity on cancer cell lines with lower IC50 values. The most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines with IC50 value of 5.3 and 6.8µM followed by compound (5) with IC50 value of 10.1 and 9.3µM, respectively. Structure-activity relationship reveals that the fluoro substituents at position C-8 while hydroxyl substituents at C-2 and C-5 positions played an important role in toxicity.

Posological Considerations of Ocimum sanctum (Tulasi) as per Ayurvedic Science and Pharmaceutical Sciences.

A study in 2010 reported that administration of 2 g of O. sanctum leaves for 30 days to laboratory male albino rabbits showed adverse effect on sperm count and male hormones. The dose and duration at which this testing was reported was commented upon as being high. It is learnt that basis this publication a few European regulators have imposed restrictions on usage of O. sanctum. Recognizing the need for evaluation, a review has been made of the posological considerations related to decision on dose of a drug in pharmaceuticals (drug development stages) and in Ayurvedic science as part of history of use and current usage. Specifically, we report the dose range as per documented tradition, marketed products containing O. sanctum as an ingredient and current clinical practice. Greater consultation is suggested before deciding the studies on Ayurvedic herbs. Regulatory action of banning use of O. sanctum needs a review and may need to be replaced with an advisory.

Management of internal hemorrhoids by Kshara karma: An educational case report.

A 66-year-old male patient came to the anorectal clinic, Outpatient department, AVT Institute for Advanced Research, Coimbatore, Tamil Nadu, with complaints of prolapsing pile mass during defecation and bleeding while passing stool. The case was diagnosed as "Raktarsha" - 11 & 7 'o' clock position II degree internal hemorrhoids, deeply situated, projecting one and caused by pitta and rakta; with bleeding tendency. Kshara karma (application of caustic alkaline paste) intervention was done in this case to internal hemorrhoids under local anesthesia. The pile mass and per rectal bleeding resolved in 8 days and the patient was relieved from all symptoms within 21 days. No complications were reported after the procedure. The patient was followed up regularly from 2004 onward till date and proctoscopic examination did not reveal any evidence of recurrence of the hemorrhoids.

Double-blind, randomized, controlled, pilot study comparing classic ayurvedic medicine, methotrexate, and their combination in rheumatoid arthritis.

OBJECTIVE: To compare classic Ayurveda, methotrexate (MTX), and their combination in a double-blind, randomized, double-dummy, pilot trial in rheumatoid arthritis (RA) for 36 weeks. METHODS: Forty-three seropositive RA patients by American College of Rheumatology (ACR) criteria with disease duration of less than 7 years were assigned to the following treatment groups: MTX plus Ayurvedic placebo (n = 14), Ayurveda plus MTX placebo (n = 12), or Ayurveda plus MTX (n = 17). Outcomes included the Disease Activity Score (DAS28-CRP), ACR20/50/70, and Health Assessment Questionnaire--Disability Index. All measures were obtained every 12 weeks for 36 weeks. Analyses included descriptive statistics, analysis of variance, χ², or Student t test. The unique features of this study included the development of placebos for each Ayurvedic pharmacological dosage form and individualization of Ayurvedic therapy. RESULTS: All groups were comparable at baseline in demographics and disease characteristics. There were no statistically significant differences among the 3 groups on the efficacy measures. ACR20 results were MTX 86%, Ayurveda 100%, and combination 82%, and DAS28-CRP response were MTX -2.4, Ayurveda -1.7, and combination -2.4. Differences in adverse events among groups were also not statistically significant, although the MTX groups experienced more adverse event (MTX 174, Ayurveda 112, combination 176). No deaths occurred. CONCLUSIONS: In this first-ever, double-blind, randomized, placebo-controlled pilot study comparing Ayurveda, MTX, and their combination, all 3 treatments were approximately equivalent in efficacy, within the limits of a pilot study. Adverse events were numerically fewer in the Ayurveda-only group. This study demonstrates that double-blind, placebo-controlled, randomized studies are possible when testing individualized classic Ayurvedic versus allopathic treatment in ways acceptable to western standards and to Ayurvedic physicians. It also justifies the need for larger studies.

Insecticidal and larvicidal activities of medicinal plant extracts against mosquitoes.

In recent years, use of environment friendly and biodegradable natural insecticides of plant origin have received renewed attention as agents for vector control because they are rich in bioactive chemicals, active against a limited number of species including specific target insects, and biodegradable. The present study was carried out to evaluate the adulticidal, repellent, and larvicidal activity of crude hexane, ethyl acetate, and methanol extracts of eight plants, viz. Aristolochia indica L., Cassia angustifolia Vahl, Diospyros melanoxylon Roxb., Dolichos biflorus L., Gymnema sylvestre (Retz) Schult, Justicia procumbens L., Mimosa pudica L., and Zingiber zerumbet L., were tested against adult and early fourth instar larvae of Culex gelidus Theobald and Culex quinquefasciatus Say (Diptera: Culicidae). The effective adult mortality was observed in methanol extract of A. indica, ethyl acetate extract of D. biflorus, and ethyl acetate and hexane extract of Z. zerumbet against C. gelidus and C. quinquefasciatus (LD(50) =37.75, 78.56, 129.44, 86.13, 80.06, 112.42, 53.83, and 46.61; LD(90) =166.83, 379.14, 521.50, 289.83, 328.18, 455.72, 181.15, and 354.50 ppm, respectively). Complete protections for 150 min were found in hexane and methanol extract of A. indica and Z. zerumbet at 1,000 ppm against mosquito bites. The highest larval mortality was found in the hexane extract of Z. zerumbet, ethyl acetate extract of D. biflorus, and methanol extracts of A. indica against C. gelidus (LC(50) =26.48, 33.02, and 12.47 ppm; LC(90) =127.73, 128.79, and 62.33 ppm) and against C. quinquefasciatus (LC(50) =69.18, 34.76, and 25.60 ppm; LC(90) =324.40, 172.78, and 105.52 ppm), respectively, after 24 h. The plant extracts are potential to be used as an ideal eco-friendly approach for the control of the Japanese encephalitis vector, C. gelidus, and lymphatic filariasis vector, C. quinquefasciatus.

On the potential of Tephrosia purpurea as anti-Helicobacter pylori agent.

AIM OF THE STUDY: Since Tephrosia purpurea (Linn.) Pers. (Fabaceae) has traditional use in curing different types of wounds including gastroduodenal ulcers, it was of interest to evaluate the in vitro anti-Helicobacter pylori activity profile of the plant extract and its fractions with a view to examining its therapeutic potential, if any. MATERIALS AND METHODS: Employing clinical isolates and standard strains of Helicobacter pylori, the extract and fractions were bioevaluated in terms of MIC and MBC values, acid stability, time-kill kinetics, drug resistance, and synergistic potential. RESULTS: The methanolic extract showed promising activity against clinical isolates and standard strains of Helicobacter pylori, including metronidazole-resistant strains. Fractionation of the extract revealed the n-hexane and chloroform fractions to possess marked activity. The extract and the less polar fractions remained functionally active in acidic condition similar to stomach environment, exhibited consistent bacteriostatic activity during repeated exposure, and demonstrated synergism, complete or partial, even with antibiotic-resistant strains. CONCLUSION: Apolar fractions of Tephrosia purpurea may have therapeutic potential in combating Helicobacter pylori mediated gastroduodenal disorders.

Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase.

The naphthoquinone 7-methyljuglone (5-hydroxy-7-methyl-1,4-naphthoquinone) has previously been isolated and identified as an active component of root extracts of Euclea natalensis which displays antitubercular activity. Herein, a series of synthetic and plant-derived naphthoquinone derivates of the 7-methyljuglone scaffold have been prepared and evaluated for antibacterial activity against Mycobacterium tuberculosis. Several of these compounds have been shown to operate as subversive substrates with mycothiol disulfide reductase. The absence of a direct correlation between antitubercular activity and subversive substrate efficiency with mycothiol disulfide reductase, might be a consequence of their non-specific reactivity with multiple biological targets (e.g. other disulfide reductases).

An efficient chemical method for separation of corsolic acid from its isomeric maslinic acid.

Based on the difference in steric bulk around C12-C13 double bond, the two isomeric dihydroxy pentacyclic triterpenic acids viz: corsolic acid and maslinic acid have been quantitatively separated via their methyl esters by reacting with the bulky m-chloroperbenzoic acid. Corsolic acid methyl ester was obtained in pure form, whereas maslinic acid methyl ester was separated as 12-oxo derivative formed via its epoxide. Alkaline hydrolysis of corsolic acid methyl ester afforded the desired acid. This method was also found to work well with the isomeric amyrin mixture (alpha- and beta-), but not highly selective. The high selectivity of this method with corsolic maslinic acid system can be rationalized in terms of 2alpha-hydroxy functionality, which provides additional crowding around the double bond and completely prevented corsolic acid from its reaction with perbenzoic acid.

Three new pentacyclic triterpenes and some flavonoids from the fruits of an Indian Ayurvedic plant Dendrophthoe falcata and their estrogen receptor binding activity.

Extensive chromatographic screening of extracts of the fruits of the Indian Ayurvedic plant, Dendrophthoe falcata, resulted in the isolation of three new triterpenes, 3beta-acetoxy-1beta-(2-hydroxy-2-propoxy)-11alpha-hydroxy-olean-12-ene (1), 3beta-acetoxy-11alpha-ethoxy-1beta-hydroxy-olean-12-ene (2) and 3beta-acetoxy-1beta-hydroxy-11alpha-methoxy-olean-12-ene (3) along with nine known compounds, 3beta-acetoxy-1beta,11alpha-dihydroxy-olean-12-ene (4), 3beta-acetoxy-1beta,11alpha-dihydroxy-urs-12-ene (5), 3beta-acetoxy-urs-12-ene-11-one (6), 3beta-acetoxy-lup-20(29)-ene (7), 30-nor-lup-3beta-acetoxy-20-one (8), (20S)-3beta-acetoxy-lupan-29-oic acid (9), kaempferol-3-O-alpha-L-rhamnopyranoside (10), quercetin-3-O-alpha-L-rhamnopyranoside (11), and gallic acid (12). The structures of these compounds were determined using 1D and 2D NMR and high resolution electrospray mass spectrometry. These compounds were assayed for binding to estrogen receptors-alpha and beta and kaempferol-3-O-alpha-L-rhamnopyranoside (10) was found to be a ligand for both receptors with greater affinity for beta. The triterpenes (1-9) are reported for the first time in the genus Dendrophthoe and assumes taxonomic significance.

A new aurone and two rare metabolites from the leaves of Diospyros melanoxylon.

A new aurone, 4,6-dihydroxy-2-[alpha,alpha-(4-hydroxyphenyl)hydroxy]methylene-3(2H)-benzofuranone (2) and two rare metabolites viz. selin-4(15)-en-1beta,11-diol (5) and 5,7-dihydroxy-3-O-beta-D-glucopyranosyl-l''' --> 6''glucopyranoside-2-{4-hydroxyphenyl}-4H-benzopyran-4-one (6) in addition to the known protocatechuic acid methyl ester (1), quercitin (3) and gallic acid (4) were isolated from the methanol extract of Diospyros melanoxylon leaves. The structures were elucidated by a combination of chemical and spectroscopic analysis. Interestingly, compound 2 was found to exist in both E- and Z-isomeric forms in a 15:85 ratio. The present isolation of compounds 2 and 5 assumes taxonomic significance as aurones and sesquiterpenes have not yet been reported from the Diospyros genus, consisting of more than 350 identified species.

Antimicrobial activity of some pentacyclic triterpenes and their synthesized 3-O-lipophilic chains.

The major metabolites of Diopsyros melanoxylon viz. amyrins and ursolic acid and their lipophilic 3-O-fatty acid ester chains (C12-C18), which are synthesized now under mild esterification conditions in excellent yields (80-95%), were evaluated for their antimicrobial activity against a series of Gram positive and Gram negative bacteria. Significantly these compounds were found to exhibit potent activity against Gram negative bacteria Pseudomonas syringae (ATCC #13457) and fairly good activity against Gram positive bacteria, Bacillus sphaericus (ATCC #14577) and Bacillus subtilis (ATCC #6051).

A new tetracyclic triterpene from the latex of Euphorbia nerifolia.

A new tetracyclic triterpene 9,19-cyclolanost-22(22'), 24-diene-3beta-ol, named as nerifoliene (2) along with euphol (1) were isolated from the fresh latex of Euphorbia nerifolia. Their structures were elucidated on the basis of spectral (IR, 1H and 13C NMR, FAB and EI Mass) data.

Antifeedant activity of some pentacyclic triterpene acids and their fatty acid ester analogues.

The 3-O-fatty acid ester derivatives (C(12)-C(18)) of two pentacyclic triterpenic acids, ursolic acid and oleanolic acid, were synthesized under mild esterification conditions in excellent yields (80-85%) and screened for their antifeedant activity, together with the parent acids, against the agricultural pest tobacco caterpillar larvae (Spodoptera litura F) in a no-choice laboratory study. The Urs-12-ene-28-carboxy-3beta-octadecanoate and olean-12-ene-28-carboxy-3beta-hexadecanoate were found to exhibit exceptionally potent antifeedant activities at 50 microg/cm(2) concentration, even after 48 h.