Pharmacology of oleanolic acid and ursolic acid

OBJECTIVE: The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity. DESIGN: This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study. RESULTS: Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoetic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound. CONCLUSION: Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted. (Altern Med Rev 2000;5(4) 334-346)

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Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review.

The locus coeruleus (LC) is the major noradrenergic nucleus of the brain, giving rise to fibres innervating extensive areas throughout the neuraxis. Recent advances in neuroscience have resulted in the unravelling of the neuronal circuits controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. The LC is a major wakefulness-promoting nucleus, resulting from dense excitatory projections to the majority of the cerebral cortex, cholinergic neurones of the basal forebrain, cortically-projecting neurones of the thalamus, serotoninergic neurones of the dorsal raphe and cholinergic neurones of the pedunculopontine and laterodorsal tegmental nucleus, and substantial inhibitory projections to sleep-promoting GABAergic neurones of the basal forebrain and ventrolateral preoptic area. Activation of the LC thus results in the enhancement of alertness through the innervation of these varied nuclei. The importance of the LC in controlling autonomic function results from both direct projections to the spinal cord and projections to autonomic nuclei including the dorsal motor nucleus of the vagus, the nucleus ambiguus, the rostroventrolateral medulla, the Edinger-Westphal nucleus, the caudal raphe, the salivatory nuclei, the paraventricular nucleus, and the amygdala. LC activation produces an increase in sympathetic activity and a decrease in parasympathetic activity via these projections. Alterations in LC activity therefore result in complex patterns of neuronal activity throughout the brain, observed as changes in measures of arousal and autonomic function.

Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organisation.

Pharmacological activities of natural triterpenoids and their therapeutic implications

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Mechanism of ulcerogenic activity of indomethacin and oxyphenbutazone.

Pharmacological studies to isolate the active constituents from Cyperus rotundus possessing anti-inflammatory, anti-pyretic and analgesic activities.

Withania somnifera, herbal rejuvenative tonic widely used by Ayurvedic physicians in India, was tested for its adaptogenic properties. Pretreatment with this drug increased the swimming endurance in mice. It prevented gastric ulcers induced chemically or by stress in rats. Milk-induced leucocytosis was also prevented in mice. The drug prevented increase in adrenal weight and decrease in ascorbic acid and Cortisol content of adrenals during stress. It appears to induce a state of non-specifically increased resistance (SNIR) during stress.

Krishna P. Bhargava

Papers

Mechanism of ulcerogenic activity of indomethacin and oxyphenbutazone.

Pharmacological studies to isolate the active constituents from Cyperus rotundus possessing anti-inflammatory, anti-pyretic and analgesic activities.

Withania Somnifera (Ashwagandha), a Rejuvenating Herbal Drug Which Enhances Survival During Stress (an Adaptogen)

Anti-inflammatory activity of taxifolin

A pharmacological study of Cyperus rotundus.