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The antioxidant activity of Withania somnifera (WS) glycowithanolides was assessed in chronic footshock stress induced changes in rat brain frontal cortex and striatum. The stress procedure, given once daily for 21 days, induced an increase in superoxide dismutase (SOD) and lipid peroxidation (LPO) activity, with concomitant decrease in catalase (CAT) and glutathione peroxidase (GPX) activities in both the brain regions. WS glycowithanolides (WSG), administered orally 1 h prior to the stress procedure for 21 days, in the doses of 10, 20 and 50 mg/kg, induced a dose-related reversal of the stress effects. Thus, WSG tended to normalise the augmented SOD and LPO activities and enhanced the activities of CAT and GPX. The results indicate that, at least part of chronic stress-induced pathology may be due to oxidative stress, which is mitigated by WSG, lending support to the clinical use of the plant as an antistress adaptogen.

The roots of Withania somnifera (WS) are used extensively in Ayurveda, the classical Indian system of medicine, and WS is categorized as a rasayana, which are used to promote physical and mental health, to provide defence against disease and adverse environmental factors and to arrest the aging process. WS has been used to stabilize mood in patients with behavioural disturbances. The present study investigated the anxiolytic and antidepressant actions of the bioactive glycowithanolides (WSG), isolated from WS roots, in rats. WSG (20 and 50 mg/kg) was administered orally once daily for 5 days and the results were compared by those elicited by the benzodiazepine lorazepam (0.5 mg/kg, i.p.) for anxiolytic studies, and by the tricyclic anti-depressant, imipramine (10 mg/kg, i.p.), for the antidepressant investigations. Both these standard drugs were administered once, 30 min prior to the tests. WSG induced an anxiolytic effect, comparable to that produced by lorazepam, in the elevated plus-maze, social interaction and feeding latency in an unfamiliar environment, tests. Further, both WSG and lorazepam, reduced rat brain levels of tribulin, an endocoid marker of clinical anxiety, when the levels were increased following administration of the anxiogenic agent, pentylenetetrazole. WSG also exhibited an antidepressant effect, comparable with that induced by imipramine, in the forced swim-induced 'behavioural despair' and 'learned helplessness' tests. The investigations support the use of WS as a mood stabilizer in clinical conditions of anxiety and depression in Ayurveda.

Ginkgolic acid conjugates (GAC) (6-alkylsalicylates, namely n-tridecyl-, n-pentadecyl-, n-heptadecyl-, n-pentadecenyl- and n-heptadecenylsalicylates) isolated from the leaves of Indian Ginkgo biloba Linn., (IGb) were tested for their putative role in anxiety in rats. Elevated plus maze, open-field behaviour, novelty-induced feeding latency and social interaction were the rodent behavioural models used in this study. GAC (0.3 and 0.6 mg/kg, each, p.o.) on single acute administration, showed dose-related changes in the behaviour. GAC (0.6 mg/kg) and DZ augmented open arm entries, the open arm/closed arm entries ratio and increased time spent in the open arm on the elevated plus maze. In the open field, GAC (0.6 mg/kg) and DZ significantly increased ambulation and reduced the immobility time. EGb 761 showed a similar profile. GAC (0.6 mg/kg) and DZ significantly attenuated the increased latency to feed in novel environment. By contrast, EGb 761 and Ginkocer further augmented feeding latency. None of the drugs tested showed any significant effect in the social interaction test. GAC showed consistent and significant anxiolytic activity in all the variables investigated. By contrast, EGb 761 and Ginkocer, which are devoid of GAC, did not evoke significant activity. However, increased rearing and decreased immobility time only in open field behaviour shown by EGb 761 may be due to some antianxiety activity of a lesser degree. Our observations suggest that GAC may be the active constituents of Ginkgo biloba responsible for the anxiolytic activity.

Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei including medial septum and the vertical limb of the diagonal band. Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A. These changes were accompanied by enhanced M1-muscarinic cholinergic receptor binding in lateral and medial septum as well as in frontal cortices, whereas the M2-muscarinic receptor binding sites were increased in a number of cortical regions including cingulate, frontal, piriform, parietal and retrosplenial cortex. Treatment with Shilajit or the defined extract from Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The data suggest that Shilajit and the defined extract from Withania somnifera affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from Withania somnifera observed in animals and humans.

Mangiferin, a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside) purified from plant sources was shown to have in vivo growth-inhibitory activity against ascitic fibrosarcoma in Swiss mice. Following in vivo or in vitro treatment, it also enhanced tumor cell cytotoxicity of the splenic cells and peritoneal macrophages of normal and tumor-bearing mice. In vitro treatment of the splenic cells of tumor-bearing mice with mangiferin resulted in augmented killing of tumor cells, both resistant and sensitive to natural killer cells. Mangiferin was also found to antagonize in vitro the cytopathic effect of HIV. The drug appears to act as a potent biological response modifier with antitumor and antiviral effect.

The effects of subcutaneous (s.c.) administration of processed shilajit (PS) alone and in combination with insulin (s.c.) on plasma glucose levels (PGL) were determined in either sex of streptozotocin-induced diabetic (SID) rats. PS (50 μg/kg ; s.c.) did not alter plasma glucose levels in SID rats. Insulin (0.25-1.0 U/kg ; s.c.), dose-dependently produced hypoglycaemia in SID rats. PS (50 μg/kg ; s.c.) potentiated and prolonged the hypoglycaemic action of insulin when administered concurrently. Chronic administration of PS (0.1-10 mg/kg ; b.i.d. for 10 days ; i.p.) had no influence per se on plasma glucose levels. Chronic administration of PS (1.0 mg/kg ; b.i.d. for 10 days ; i.p.) prevented the streptozotocin (STZ)-induced diabetes in rats, whereas a relatively lower (0.1 mg/kg ; b.i.d. for 10 days ; i.p.) and significantly higher dose (10 mg/kg ; b.i.d. for 10 days ; i.p.) of PS had no influence on the STZ-induced diabetes. The results suggest that administration of PS along with insulin would potentiate the insulin-induced hypoglycaemia, and chronic administration of a carefully determined dose of PS would inhibit the development of STZ-induced diabetes.

The dose- and time-dependent effects of processed shilajit (SJP) on morphometric and functional changes of mouse peritoneal macrophages were evaluated. Several dynamic aspects of cellular modulations were observed in response to SJP treatment (0.025–900 mcg per mouse, i.p.) for different periods of time (0 min to several hours). A plausible mechanism of drug-receptor interactions, involving different types of transition states, is postulated. Dose and time dependent bond formation-deformation in the complex transitions were reflected in the morphometric and functional manifestations of the adherent cells. These findings suggest the necessity of carefully determining the dose and period of administration of shilajit even when accepted as a panacea.

The active principles of Withania somnifera (WS, 20–50 mg/kg, p.o.), consisting of equimolar amounts of sitoindosides. VII–X and withaferin A, were investigated for putative nootropic activity in an experimentally validated Alzheimer's disease (AD) model. The syndrome was induced by ibotenic acid (IA) lesioning of the nucleus basalis magnocellularis (NBM) in rats. Cognitive deficits induced in NMB-lesioned rats were assessed by attenuation of a learned active avoidance task and a decrease in frontal cortical and hippocampal acetylcholine (ACh) concentrations, choline acetyltransferase (ChAT) activity and muscarinic cholinergic receptor (MCR) binding. IA-induced NBM lesioning in rats caused a marked cognitive deficit, as evidenced by severe reduction of the learned task, and was accompanied by a significant decrease in frontal cortex and hippocampal ACh levels, ChAT activity and MCR binding. WS (50 mg/kg) significantly reversed both IA-induced cognitive deficit and the reduction in cholinergic markers after 2 weeks of treatment. The findings validate the medharasayan (promoter of learning and memory) effect of W. somnifera, as has been reported in Ayurveda.

The radicophilicity (antiradical-antioxidant effects) of processed shilajit (SJP) to oxygen-derived free radicals and nitric oxide (NO), and the attendant H 2 O 2 cleaving effect were evaluated. SJP provided complete protection to methyl methacrylate (MMA) against hydroxyl radical-induced polymerization and acted as a reversible NO-captodative agent. SJP (20 and 50 mg/kg/day, i.p., for 21 days) induced a dose-related increase in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities in frontal cortex and striatum of rats. The data were comparable to those of (-)-deprenyl (2 mg/kg/day, i.p., for 21 days) in respect of SOD and CAT activities. These findings are consistent with the therapeutic uses of shilajit as an Ayurvedic rasayan (rejuvenator) against oxidative stress and geriatric complaints

Department of Chemistry, Ramakrishna Mission Residential College Narendrapur, Kolkata-700 103, India E-mail : pulakganguly@yahoo.co.in Natreon-Inc. (India), CL-18A, Salt Lake, Kolkata-700 091, India Manuscript received 01 June 2009, accepted 21 June 2010 A new chemotype of Ocimum sanctum bearing high terpene constituents of immunomodulatory potential has been discovered.

Mangiferin, a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside), isolated from several plant sources, was shown to be effective in activating murine peritoneal macrophages. It acted as a strong inducing agent with a peak elicitation response at 48 h interval of treatment (10 μg mangiferin/g body weight, g b.w). The mangiferin-elicited, as well as in vitro mangiferin-treated, macrophages showed increased lysosomal enzyme acid phosphatase activity and enhanced cytotoxicity, and phagocytosis against ascitic fibrosarcoma (AFS) cells. The augmented tumour killing activities were associated with enhanced tumour target binding by the macrophages. However, the in vivo effect of mangiferin in activating macrophages was of short duration.

Convincing evidence has been found for the similarities in physical and chemical characteristics of shilajit and soil humus. Structural similarities of building blocks of the humus core of shilajit and two soil samples have been established by acid hydrolysis of the extracted humus (EHs; free from loosely-bound low M r organic compounds), followed by comprehensive Chromatographic (HPTLC) and spectroscopic (u.V., [ 1 H]NMR, GC, MS) analyses of the degradation products. 13 C-isotopic abundane data of the core molecules, as determined from their respective (M + 1) values, in the EI MS, suggest that the origin of these molecules in shilajit, at least in part, predates their biological synthesis (e.g. by plant-microbial interaction). Additional evidence has been found in support of this contention. A memory molecule (1 and its hemiquinone complement, 5a ag 5b ), that exhibited appropriate chemical and biological properties has been encountered in the core of all humus samples.

Effects, in albino rats, of a processed shilajit (Sh-P), native shilajit (Sh-N) (unprocessed water-soluble fraction), and a preparation consisting of a mixture of ethyl acetate extractives (EE) and fulvic acids (FAs) from Sh-P, were evaluated in (i) an active avoidance, (ii) elevated plus-maze and (iii) open-field behaviour paradigms. This study was undertaken to appraise the validity of use of shilajit as an Ayurvedic medha rasayan (enhancer of learning and memory). Sh-P and its active constituents (EE-FAs) significantly augmented learning acquisition and memory retrieval in the battery of tests, designed for this purpose, according to accepted tenets. Sh-N, on the other hand, produced erratic responses (both augmentative and retardative) in the above parameters. The U-shaped dose-responses shown by Sh-P and EE-FAs are reminiscent of agents that improve cognitive functions. Additionally, Sh-P and EE-FAs, in high doses (25–50 mg/kg p.o.), produced significant antianxiety effect in the open-field behaviour test. The present and earlier findings seem to suggest that the action of shilajit is mediated by facilitating communication between the immune and the central nervous systems. These findings reinforce our earlier postulate that purification of shilajit is an imperative necessity to ensure its optimum therapeutic effect. This would also safeguard from potential health risks associated with prolonged ingestion of raw shilajit containing free radicals and fungal toxins.

Glycowithanolides, consisting of equimolar concentrations of sitoindosides VII-X and withaferin A, isolated from the roots of Withania somnifera Dunal, have been reported to have an antioxidant effect in the rat brain frontal cortex and striatum. In the present study, the effect of 10 days of oral administration of these active principles, in graded doses (10, 20 and 50 mg/kg), was noted on iron overload (FeSo(4), 30 mg/kg, i.p.) induced hepatotoxicity in rats. Apart from hepatic lipid peroxidation (LPO), the serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, were assessed as indices of hepatotoxicity. Silymarin (20 mg/kg, p.o.) was used for comparison. Iron overload induced marked increase in hepatic LPO and serum levels of the enzymes, which was attenuated by WSG in a dose-related manner, and by silymarin. The results indicate that the reported use of WS in Ayurveda for hepatoprotection against heavy metals and other environmental toxins, may be due the antioxidant action of WSG.

Shilajit, a panacea of oriental medicine, collected from different countries, exhibits overtly different levels of bioactivity. The effects of shilajit, collected from India, Nepal, Pakistan and Soviet Russia, and the effects of organic constituents isolated from a potent shilajit sample, were studied in a number of antistress and CNS activity paradigms. Shilajit from Kumaon (India), Dolpa (Nepal), and a combintion (1:1) of the total ethylacetate extracts (TE) and fulvic acids (FAs), from Kumaon shilajit, produced statistically significant effects in forced swimming-induced immobility in albino mice; restraint stress and aspirin-induced gastric ulcers in pylorus ligated albino rats; and augmented the learning acquisition and memory retention in old rats. The potential risk of ingesting shilajit, in the native form as a ‘health product’, was appraised in view of its high stable free radical content and possible contamination with mycotoxin-producing fungi. Hence, there is an imperative need for formulation of shilajit on the basis of its isolated active constituents (TE and FAs). Additionally, the physical and spectral characteristics of active FAs (bioactivity-directed) were determined and compared with those of less active and inactive samples. These would provide predictability for selection of FAs for formulation of shilajit.

The nature of the building blocks and their alignments in the humus 'core' of shilajit were determined by mild and drastic degradations and by comprehensive spectroscoplc analyses of the products. Mild hydrolysis of humic acids (HAs) from shilajit afforded two new dibenzo-a-pyrones, viz. 3-O-palmitoyl-8-hydroxydibenzo-α-pyrone (1) and 3-O-β-d-glucosyl-8-hydroxydibenzo-α-pyrone (2), and two new tirucallane-type triterpenic acids, viz. 24(Z)-3β-hydroxy-tirucalla-8,24-dien-26-oic acid (3) and 24(Z)-3β-hydroxy-tirucalla-7,24-dien-26-oic acid (4). The resistant HAs (RHAs), obtained after mild hydrolysis, when subjected, separately, to KMnO4 oxidation and Zn dust distillation gave several aromatic carboxylic acids, polynuclear aromatic hydrocarbons, a simple dibenzo-α-pyrone (= 3,4-benzo-coumarin) and fluorene. These products, except the two last-named compounds, have been reported from similar degradations of soil-sediment humus indicating the inherent structural similarities of humus from two dissimilar sources. On the basis of the above and related observations, a partial structure of the shilajit humus core, involving oxygenated dibenzo-α-pyrones, is postulated. Additionally, the necessity of standardization of shilajit, a panacea in oriental medicine, on the basis of its active principles and carrier molecules (e.g. fulvic acids, FAs) is suggested.

Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700 032, India R & D Centre, Indian Herbs Ltd., Saharanpur-247 001, Uttar Pradesh, India E-mail : vishnu20024@rediffmail.com Manuscript received 3 September 2008, accepted 1 October 2008 Antioxidant capacity of an array of free and conjugated phytosteroids of Solanum xanthocarpum and Solanum nigrum, and withasteroids of Withania somnifera has been assessed. Four standard sets of assays, namely, reduction of ABTS, DPPH, FRAP and superoxide radical, have been used. The contribution, in this regard, of metal ions, naturally - complexed with the phytosteroids and withasteroids, has also been evaluated. The findings suggest the contribution of naturally occurring metallo-organic complexes in human well being. The mechanisms suggested for the antioxidant actions of the compounds project the role of molecular architecture of free and conjugated steroids. Some other beneficent actions of these compounds, e.g. systemic lowering of cholesterol and LDL, and the selective inhibition of COX-2 by sitoindosideindolealkylamine- conjugated withasteroids, are noteworthy. The last-named compound(s) contribute also to the adaptogenic activity of W. somnifera.

R & D Centre, Indian Herbs Ltd., Saharanpur-247 00 I, Uttar Pradesh, India E-mail : vishnu20024@rediffmail.com Manuscript received 5 August 2008, accepted 12 August 2008 A unified manifestation of the macrocosmic and microcosmic actions is expressed by the co-occurrence of C60- fullerene-dibenzo-α-pyrone (DBP) conjugates in meteorites, ammonites, and Shilajit. The crystal forms of mineral (aragonite) deposition in ammonites (the major marine precursors of Shilajit), are distinctly different in many respects from the inorganic mineral, aragonite. The mineral deposition in the living ammonite shells is under strict biological control and involves organo-mineral complexes received from meteorites. These constituents in ammonites arc eventually transformed into Shilajit by humification. Hence, the supramolecular assemblies of complex chemical constituents of ammonites, in many respects, show striking similarities with the humic constituents (FAs, HAs and HMs) of meteorites and of Shilajit. Some selected assemblies, viz. fusoms and DCPs, of Shilajit, comprising of fullercne-DBP conjugates in their inner core, were found to confer facile water-solubility, stability and superior bioavailahility (Yogabahi in Ayurveda) to a host of chemical agents that are ordinarily water-insoluble, thermolabile, autoxidizable, and/or prematurely biodegradable before reaching the target site. The potential of this superior drug delivery system is evaluated.

"Shilajit" is a panacea in Ayurveda, the Indian traditional system of medicine. The major bioactives of "shilajit" have been identified as dibenzo-α-pyrones (DBPs), its oligomers and aminoacyl conjugated derivatives. These bioactive compounds play a crucial role in energy metabolism in all animal cells including those of man. 3-hydroxydibenzo-α-pyrone (3-OH-DBP), a key DBP component of "shilajit" is converted, among other products, to another active DBP derivative, viz. 3,8-hydroxydibenzo-α-pyrone, 3,8(OH) 2 -DBP, in vivo , when its precursor is ingested. 3,8(OH) 2 -DBP is then involved in energy synthesis in the mitochondria in the reduction and stabilization of coenzyme Q 10 in the electron transport chain. As the chemical synthesis of 3,8(OH) 2 -DBP is a complex, multi-step process and economically not readily viable, we envisioned the development of a process using microorganisms for bioconversion of 3-OH-DBP to 3,8(OH) 2 -DBP. In this study, the biotransformation of 3-OH-DBP is achieved using Aspergillus niger , which was involved in the humification process on sedimentary rocks leading to "shilajit" formation. A 60% bioconversion of 3-OH-DBP to 3,8(OH) 2 -DBP and to its aminoacyl derivatives was achieved. The products were characterized and estimated by high performance liquid chromatography (HPLC), high performance flash chromatography (HPFC) and gas chromatography-mass spectrometry (GC-MS) analyses. Among the Aspergillus species isolated and identified from native "shilajit", A. niger was found to be the most efficient for this bioconversion.

The biochemical role of free and conjugated alkaloids in the fruits of Crinum asiaticum during strees (incisional injury and attack by an insect) is appraised. Wounding of C. asiaticum fruits caused almost complete hydrolysis of the alkaloidal conjugates and also produced oxidized metabolises of lycorine and its analogues. Prior treatment of fruits with anaesthetic agents, e.g. ether and lidocaine, not only protected the alkaloidal conjugates from hydrolysis but also prevented their oxidation. The qualitative and quantitative changes observed in the alkaloids, in response to the stress, suggest their role in protective and repair mechanisms of the producer plant, notably, augmentation of a ‘second messenger‘, cAMP, in the fruits in response to injury and systemic administration of theophylline was observed. Prior administration of anaesthetic agents (ether or lidocaine), kept the concentration of cAMP significantly low despite inflicting subsequent injury.

The chemical polemics in the reported literature on shilajit are resolved. This study shows that humification of latex and resin-bearing plants is responsible for the major organic mass (80-85%) of shilajit. The low mol. wt. chemical markers (&lo%), viz. aucuparins, oxygenated dibenzo-K -pyrones and triterpenic acids of the tirucallane type (free and conjugated), occurring in the core structure of shilajit humus, are the major active constituents of Himalayan shilajit. The therapeutic effects of shilajit are the consequences of hormonal control and regulation of immunity.

Effects of glycowithanolides (Ws, 10–150 mg/kg, i.p.), consisting of sitoindosides VII-X, in combination with withaferin-A, from Withania somnifera, in Swiss mice were evaluated on (i) morphine-induced inhibition of gastrointestinal tract (GIT) transit and (ii) development of tolerance to morphine-induced analgesia. Pretreatment with Ws significantly reversed the morphine (5 mg/kg, s.c.)-induced inhibition of GIT transit at all doses. Ws (100 mg/kg, i.p., o.d., for 10 days) significantly inhibited the development of tolerance to morphine-induced analgesia. Ws per se did not influence the intestinal motility nor did it produce any perceptible analgesic effect. The present and earlier findings with Ws suggest its potential in alleviating the adverse effects of morphine and the attendant immunodepression.

The effect of processed shilajit (SJ-P) was evaluated on murine peritoneal macrophages and on the cohabiting fibroblasts. The study revealed a dynamic aspect of modulation of the peritoneal cells by SJ-P (200–600 mcg/mouse), when administered intraperitoneally. The findings further suggested that by carefully determining the dose, SJ-P can be used in wound healing and in related inflammatory disease states.

Effects of concomitant administration of Processed Shilajit (PS, 0.1 and 1 mg/kg, i.p.), in Swiss mice were evaluated on the development of tolerance to morphine induced analgesia in the hot plate test. Chronic administration of morphine (10 mg/kg, i.p., b.i.d.) to mice over a duration of 10 days resulted in the development of tolerance to the analgesic effect of morphine. Concomitant administration of PS with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine (10 mg/kg, i.p.) induced analgesia. Processed Shilajit per se, in the doses used, did not elicit any significant analgesia in mice; nor did the chronic concomitant administration of Processed Shilajit alter the morphine-induced analgesia. These findings with Processed Shilajit indicate its potential as a prospective modifier of analgesic tolerance to morphine.

Drug Research and Development Centre, 1078 Jessore Road, Calcutta-700 028, India Manuscript received 28 October 1999 Research in Ginkgo biloba : Recent developments

Formerly, Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Banaras Hindu University, Varanasi-221 005 Manuscript received 10 September 1997 A fundamental problem of tracing the sequence of primordial organic chemistry is the identification of the primitive organic molecules, from among the currently known millions of possible compounds. The observed intimate association, for ages, of a selected group of organic compounds, e.g. hydroxyacetophenones and oxygenated dibenzo-α-pyrones (DBPs), and of the Ayurvedic maharasas (inorganic minerals), in their natural habitats, is regarded as a strong circumstantial evidence in support of an organized sequence of primordial organic chemistry. These phenolic compounds also occur, selectively and consistently within the core of 'till' and boulders of the Gangotriglacier (1 to 60 million-year-old). Another unique feature of these compounds is that the DBPs are found in the organ deposits of several insects (baemolymph gland), animals (scent-gland, clover-stone), and in man (kidney and gall stone), bot rarely so in plants. This phenomenon suggests their non-photosynthetic (abiotic) origin, at least partly, which is also supported from their high δ 13C values. These organic compounds seem to bear a link between the primordial and the modern eras of organic chemistry on earth.

Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Banaras Hindu University, Varanasi-221 005 Manuscript recevied 29 September 1993 The chemical nature and composition of the odorous constituents of shilajit, from six countries, were determined. Collection of the volatiles from the headspace by a special technique, followed by GC MS and CI MS analyses showed the presence and relative abundance of about two dozen compounds common to all shilajit samples, albeit in different proportions. These compounds belonged to four distinct classes, viz. (i) long-chain aliphatic hydrocarbons and their derivatives at different states of oxidation, (ii) naphthenes (alkylated cycloalkanes), (iii) alkylated aromatics and phenolics and (iv) heterocyclics. Phospholipids of shilajit, isolated and characterised by selective chemical treatment and FAB MS analysis, contributed (as fixerators) to the stability of its odour. This study dispels the age-old myth regarding the composition of the 'typical' odour and reaffirms our earlier postulate about the origin of shilajit. &nbsp

Background: Chromium chelates/complexes are widely used as nutritional supplements to redress complications of type 2 diabetic mellitus (T2DM) patients. However, most of these chelates could be susceptible to oxidation into toxic Cr(VI) state. Complexation of Cr (III) with gallo-ellagi tannoids produces a herbochromium supplement (HCrS) that maintains its Cr3+ oxidation state under oxidizing circumstances in vitro. It was tested with conventional oral hypoglycemic drugs [(oral antidiabetic drugs (OAD)] for its beneficial effects in T2DM patients. Objective: A randomized clinical study with three OADs with or without HCrS was carried out in T2DM patients to evaluate the efficacy of the HCrS supplement. Materials and Methods: 150 T2DM patients were randomized into six treatment groups. After 60 days of treatment, fasting blood glucose and post-prandial blood glucose (FBG and PPBG, respectively), HbA 1c , HsCRP, oxidized low density lipoprotein (LDL), and urinary microalbumin levels and other diabetic symptoms were evaluated. Statistical Analysis: Findings were compared using one-way analysis of variance (ANOVA) with post hoc pairwise comparisons of groups using the least significant difference method. Results: Better control of FBG and PPBG levels were observed in patients receiving HCrS (−12.4 to −16.6%) compared to placebo groups (−3.4 to −9.4%). There was a 5.5–7.4% decrease in HsCRP and LDL levels in patients receiving HCrS, which is better than placebo treated groups. Significant decrease in urinary microalbumin level was observed in patients receiving HCrS (−20.0 to −22.5%) compared to placebo groups (−7.8 to

Shilajit (25 and 50 mg/kg i.p. for 5 days) significantly lowers the levels of 5HT and 5HIAA and increases the levels of DA, NA and their metabolites, in concert, in rat brain. The finding is appraised in view of its use as an Ayurvedic rasayan (rejuvenator).

Two polyoxygenated chromones, 5,7-dihydroxy-2-methylchromone (1) and 5,6-dihydroxy-7- methoxy-2-methylchromone(2), and a glucosyloxychromone, 7

Two new types of alkaloidal conjugates, a C 16 -acyloxy derivative, named palmilycorine, and an acylglucosyloxy derivative, named lycoriside, were isolated from the fruits of Crinum asiaticum . The presence of these compounds was also detected in the fleshy scale leaves and in roots of this species. The structures of the two compounds were established as 1- O -palmitoyllycorine (1) and lycorine-1- O -(6′- O -palmitoyl-β- D -glucopyranoside)(2), respectively, on the basis of chemical transformation and comprehensive spectral evidence. The biological effects of the alkaloids were evaluated.

Chinensin, a 1-aryl-2,3-naphthalide lignan, was isolated from Polyqala chinensis . Chemical transformation and UV, IR, PMR and MS evidence established its structure as 6,7-methylenedioxv-]-(3′,4′-dimethoxyphenyl)-3-hydroxymethylnaphthalene-2-carboxylic acid lactone. The lignan has not be en encountered before in nature or prepared synthetically.

Four new alkaloidal phospholipids, 2-O-glycerophosphoryllycorine, phosphatidyllycorines, phosphatidylpseudolycorines and phosphatidyllycorinium methocation, were isolated from the flowers of Zephyranthes flava. The structures of these compounds were established by comprehensive spectral analyses, chemical transformations and synthesis, where possible. The biological profile of this novel group of alkaloidal conjugates is appraised.

A new Schiff's base, named isocraugsodine, was isolated from the fruits of Crinum asiaticum . Its N -(3- methoxy-4-hydroxybenzylidene)- 4′-hydroxyphenethylamine structure was assigned on the basis of chemical trans- formation and comprehensive spectroscopic evidence. The temperature-gradient distribution of the three isomeric forms ( 1a ⇌ 1b ⇌ 1c ) of the Schiff's base was determined by high resolution 1 H NMR analysis. Isocraugsodine is considered as a direct precursor to Amaryllidaceae alkaloids.

Two new dimethoxy-acetophenone- O -glucosides and the known 2,4,6-trimethoxyacetophenone were isolated from the flowering bulbs and pseudo-stem fluid of Pancratium biflorum . The structures of the new compounds were established as 4,6-dimethoxyacetophenone-2- O -β- d -glucoside and 2,6-dimethoxyacetophenone-4- O -β- d -glucoside on the basis of chemical transformation, comprehensive spectroscopic analyses, and synthesis of the aglucones. The biological activity profile of the glucosides and their aglucones is also appraised.

The whole plant of Swertia hookeri , collected at flowering has been shown to contain two tri- and nine tetraoxygenated free, glucosyloxy, and stearyl ester xanthones and one flavonol stearyl ester. Among these, three are previously unreported in nature and one was known previously only as a synthetic compound. The xanthones are based on 1,3,5,-, 1,3,5,8- and 1,3,7,8-oxygenated systems with the middle oxygenation pattern predominating. The two ester compounds appeared only at the flowering stage. Plants collected at the pre-flowering stage gave the corresponding free compounds. The biochemical and biological significance of these findings are appraised.

Two new acylsterylglucosides, sitoindoside VII and sitoindoside VIII, were isolated from the roots of Withania somnifera Dun., and were screened for putative anti-stress activity because the plant is widely regarded as the ‘Indian Ginseng’ by practitioners of the traditional Indian system of medicine. Since an acceptable paradigm of pharmacological tests for anti-stress screening has yet to be evolved, a battery of tests were employed to delineate the activity of the test compounds. The total MeOH-H2O (1:1) extractives of the roots of W. somnifera (SG-1) and equimolecular combination of sitoindosides VII, VIII and withaferin-A, a common withanolide, (SG-2), exhibited significant anti-stress activity in all the test parameters used. The two sitoindosides also produced per se anti-stress activity, which was potentiated by withaferin-A. A preliminary acute toxicity study indicated that the compounds have a low order of acute toxicity. The anti-stress activity of SG-1 and SG-2 is consonant with the therapeutic use of W. somnifera in the Ayurveda, the Indian system of medicine.

A rare incidence of phanerogamic parasitism of Imperata cylindrica on Pancratium biflorum and the concomitant changes in the chemical constituents, from the hypersensitive responses in the host species, are reported.

The whole plant of Hoppea dichotoma has been shown to contain eleven xanthones, two flavanones and two flavones, as major chemical entities, five of which are new naturally occurring compounds. Additionally, four known triterpenes, gluanone, gluanol, friedelin and friedelin-3β-ol, have been isolated as minor entities. The taxonomic significance of the chemical characters of H. dichotoma , which are closely similar to those of Canscora decussata , is appraised.

The naturally occurring free and glycosylated flavans are reviewed. The distribution, methods of isolation and structure elucidation of flavans, by comprehensive spectral analyses, are presented. Biological properties of flavans are appraised.

Two new glycowithanolides, sitoindoside IX (1) and sitoindoside X (2), isolated from Withania somnifera Dun., were evaluated for their immunomodulatory and CNS effects (anti-stress, memory and learning) in laboratory animals, because the plant extract is used by practitioners of the Indian systems of medicine for similar purposes. The two compounds, in doses of 100–400 μg/mouse, produced statistically significant mobilization and activation of peritoneal macrophages, phagocytosis and increased activity of the lysosomal enzymes secreted by the activated macrophages. Both these compounds (50–200 mg/kg p.o.) also produced significant anti-stress activity in albino mice and rats and augmented learning acquisition and memory retention in both young and old rats. These findings are consistent with the use of W. somnifera, in Ayurveda, to attenuate cerebral function deficits in the geriatric population and to provide non-specific host defence.

The whole plant of Swertia purpurascens Wall. (Gentianaceae) has been shown to contain five tetraoxygenated and three pentaoxygenated xanthones. These are identified as 1,5,8‐trihydroxy‐3‐methoxyxanthone, 1,3,8‐trihydroxy‐5‐methoxyxanthone, 1‐hydroxy‐3,7,8‐trimethoxyxanthone, 1,3,7,8‐tetrahydroxyxanthone, 1,3,5,8‐tetrahydroxyxanthone, and 1‐hydroxy‐3,4,7,8‐tetramethoxyxanthone by chemical and spectral evidence. Additionally, the crude mixture of natural xanthones has been shown to include two partially methylated pentaoxygenated xanthones as minor entities, which yield 1‐hydroxy‐3,4,7,8‐tetramethoxyxanthone and 1‐hydroxy‐3,4,5,8‐tetramethoxyxanthone on methylation. This is the first time that pentaoxygenated xanthones have been found in a member of the genus Swertia. 1‐Hydroxy‐3,4,7,8‐tetramethoxyxanthone was previously known only as a synthetic compound. The total xanthones of S. purpurascens produce significant CNS stimulant actions, consistent with some therapeutic uses of the plant extract in the Indian system of medicine. The chemotaxonomic significance of the cooccurrence of various biogenetically related chemical characters in a single plant species is appraised.

From fluids of flower stems and bulbs, and from extracts of roots of Pancratium biflorum , collected at different stages of growth, three new glucosyloxy alkaloids, viz. hordenine-4- O -β- d -glucoside, lycorine-1- O -β- d -glucoside and pseudolycorine-1- O -β- d -glucoside, have been isolated and characterized. Additionally, three proto alkaloids, β-phenethylamine, tyramine and hordenine, together with four true alkaloids, lycorine, pseudolycorine, pretazettine and tazettine, encountered before in other memebrs of the Amaryllidaceae, have now been isolated also from this species. Ontogenic variations of alkaloidal constituents have been observed. The ability of the alkaloidal constituents to complex with divalent metal ions and phytosterols has been examined with a view to evaluating their significance in plant biochemistry.