Epidemiological evidence suggests that flavonoids may play an important role in the decreased risk of chronic diseases associated with a diet rich in plant-derived foods. Flavonoids are also common constituents of plants used in traditional medicine to treat a wide range of diseases. The purpose of this article is to summarize the distribution and biological activities of one of the most common flavonoids: luteolin. This flavonoid and its glycosides are widely distributed in the plant kingdom; they are present in many plant families and have been identified in Bryophyta, Pteridophyta, Pinophyta and Magnoliophyta. Dietary sources of luteolin include, for instance, carrots, peppers, celery, olive oil, peppermint, thyme, rosemary and oregano. Preclinical studies have shown that this flavone possesses a variety of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial and anticancer activities. The ability of luteolin to inhibit angiogenesis, to induce apoptosis, to prevent carcinogenesis in animal models, to reduce tumor growth in vivo and to sensitize tumor cells to the cytotoxic effects of some anticancer drugs suggests that this flavonoid has cancer chemopreventive and chemotherapeutic potential. Modulation of ROS levels, inhibition of topoisomerases I and II, reduction of NF-kappaB and AP-1 activity, stabilization of p53, and inhibition of PI3K, STAT3, IGF1R and HER2 are possible mechanisms involved in the biological activities of luteolin.

Distribution and biological activities of the flavonoid luteolin.

This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guarana), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed.

Plants and the central nervous system

Effect of extraction methods on yield, phytochemical constituents and antioxidant activity of Withania somnifera

Withania somnifera, popularly known as Ashwagandha is widely considered as the Indian ginseng. In Ayurveda, it is classified as a rasayana (rejuvenation) and expected to promote physical and mental health, rejuvenate the body in debilitated conditions and increase longevity. Having wide range of activity, it is used to treat almost all disorders that affect the human health. The present review discusses the pharmacological basis of the use of W. somnifera in various central nervous system (CNS) disorders, particularly its indication in epilepsy, stress and neurodegenerative diseases such as Parkinson's and Alzheimer's disorders, tardive dyskinesia, cerebral ischemia, and even in the management of drug addiction.

Withania somnifera: an Indian ginseng.

Oral administration of Eclipta alba leaf aqueous extract enhances the non-specific immune responses and disease resistance of Oreochromis mossambicus.

The practitioners of the traditional Indian system of medicine regard Withania somnifera Dun. as the 'Indian ginseng'. A new withanolide-free aqueous fraction was isolated from the roots of this plant and was evaluated for putative antistress activity against a battery of tests such as hypoxia time, antifatigue effect, swimming performance time, swimming induced gastric ulceration and hypothermia, immobilization induced gastric ulceration, autoanalgesia and biochemical changes in the adrenal glands. This bioactive fraction exhibited significant antistress activity in a dose-related manner in all the parameters studied. The extract of Withania somnifera root (a commercial preparation available locally) was used to compare the results. A preliminary acute toxicity study in mice showed a good margin of safety.

Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun.

Hepatoprotective effects of Eclipta alba on subcellular levels in rats

The alcoholic extract of fresh leaves of the plant Eclipta alba (Ea), previously reported for is hepatoprotective activity was fractionated into three parts to chemically identify the most potent bioactive fraction. The hepatoprotective potential of the fraction prepared from extract was studied in vivo in rats and mice against carbon tetrachloride induced hepatotoxicity. The hepatoprotective activity was determined on the basis of their effects on parameters like hexobarbitone sleep time, zoxazolamine paralysis time, bromosulphaline clearance, serum transaminases and serum bilirubin. Fraction EaII (10-80 mg/kg, p.o.) containing coumestan wedelolactone and desmethylwedelolactone as major components with apigenin, luteolin, 4-hydroxybenzoic acid and protocateuic acid as minor constituents exhibited maximum hepatoprotective activity and is the active fraction for hepatoprotective activity of Eclipta alba leave. The acute toxicity studies have shown that like Ea, Fraction EaII also high safety margin.

In vivo hepatoprotective activity of active fraction from ethanolic extract of Eclipta alba leaves.

An alcoholic extract of freshly collected Eclipta alba exhibited dose-dependent (62.5–500.0 mg/kg p.o.) significant hepatoprotective activity against carbon tetrachloride-induced liver injury in rats and mice. It indicated its protective role on parameters such as hexobarbitone-induced sleep, zoxazolamine-induced paralysis, bromosulphalen (BSP) clearance, serum levels of transaminases, bilirubin and protein. The extract did not show any signs of toxicity and the minimum lethal dose was greater than 2.0 g/kg when given orally and intraperitoneally in mice.

Hepatoprotective effect of ethanolic extract of Eclipta alba on experimental liver damage in rats and mice

The effects of an orally administered fraction (TB5) from the fruits of Terminalia belerica in experimental liver injury induced by carbon tetrachloride (CCI4) were studied. Hexobarbitone-induced sleep, zoxazolamine-induced paralysis, transaminases, bilirubin, total protein in serum and microsomal lipid peroxidation and triglycerides in liver were used as indices of liver injury.



A significant hepatoprotective effect was observed as evident from shortened hexobarbitone ‘sleep time’ and zoxazolamine ‘paralysis time’ when compared with CCI4 alone. Pre- and post-treatment of TB5 reduced, in a dose dependent manner, the elevated levels of serum tranaminases and bilirubin in rats, thus demonstrating its effect both as a prophylactic and curative. Its protective effects on microsomal lipid peroxidation and triglycerides in liver suggest a restorative effect in the process of CCI4-induced liver damage. TB5 did not show any signs of toxicity up to oral doses of 3.2 g/kg in mice.

K. K. Anand

Papers

Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun.

Hepatoprotective effects of Eclipta alba on subcellular levels in rats

In vivo hepatoprotective activity of active fraction from ethanolic extract of Eclipta alba leaves.

Hepatoprotective effect of ethanolic extract of Eclipta alba on experimental liver damage in rats and mice

Hepatoprotective studies of a fraction from the fruits of Terminalia belerica Roxb. on experimental liver injury in rodents