Dhawan Bn

In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica

The activity of asiaticoside, isolated from Centella asiatica, has been studied in normal as well as delayed-type wound healing. In guinea pig punch wounds topical applications of 0.2% solution of asiaticoside produced 56% increase in hydroxyproline, 57% increase in tensile strength, increased collagen content and better epithelisation. In streptozotocin diabetic rats, where healing is delayed, topical application of 0.4% solution of asiaticoside over punch wounds increased hydroxyproline content, tensile strength, collagen content and epithelisation thereby facilitating the healing. Asiaticoside was active by the oral route also at 1 mg/kg dose in the guinea pig punch wound model. It promoted angiogenesis in the chick chorioallantoic membrane model at 40 microg/disk concentration. These results indicate that asiaticoside exhibits significant wound healing activity in normal as well as delayed healing models and is the main active constituent of Centella asiatica.

Asiaticoside-induced elevation of antioxidant levels in healing wounds.

Asiaticoside derived from the plant Centella asiatica is known to possess good wound healing activity. Enhanced healing activity has been attributed to increased collagen formation and angiogenesis. Since antioxidants have been reported to play a significant role in the wound healing process we studied the effect of asiaticoside on the levels of certain antioxidants in the wound so as to explore the possible involvement of such a mechanism in the asiaticoside induced wound healing. Asiaticoside application (0.2%, topical) twice daily for 7 days to excision‐type cutaneous wounds in rats led to increased enzymatic and non‐enzymatic antioxidants, namely superoxide dismutase (35%), catalase (67%), glutathione peroxidase (49%), vitamin E (77%) and ascorbic acid (36%) in newly formed tissues. It also resulted in a several fold decrease in lipid peroxide levels (69%) as measured in terms of thiobarbituric acid reactive substance. However, continued application for 14 days showed no significant difference in these antioxidants compared with their values in vehicle treated wound tissue. It appears from the present study that asiaticosides enhanced induction of antioxidant levels at an initial stage of healing which may be an important contributory factor in the healing properties of this substance. Copyright

Andrographolide protects rat hepatocytes against paracetamol-induced damage.

Andrographolide, the active constituent isolated from the plant Andrographis paniculata, showed a significant dose dependent (0.75-12 mg/kg p.o. x 7) protective activity against paracetamol-induced toxicity on ex vivo preparation of isolated rat hepatocytes. It significantly increased the percent viability of the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It completely antagonized the toxic effects of paracetamol on certain enzymes (GOT, GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells. Andrographolide was found to be more potent than silymarin, a standard hepatoprotective agent.

Effect of Bacopa monniera Linn. (Brāhmi) extract on avoidance responses in rat

Brahmi (Bacopa monniera Linn.) is a reputed nerve tonic in Ayurvedic literature. Hence its effects on the learning performance of rats have been studied in different conditioning schedules by administering an aqueous suspension of an alcoholic extract (40 mg/kg, p.o.) for three or more days. The first schedule induced a labile behaviour using a shock-motivated brightness-discrimination reaction. The brahmi-treated group showed better acquisition, improved retention and delayed extinction (p is less than 0.01-0.05). Similarly, in an active conditioned flight reaction, the drug-treated animals showed a shorter reaction time than the controls (p less than 0.01). Also in the continuous avoidance response the drug-treated group performed better than the controls (p less than 0.01-0.05). Our findings are in conformity with the Ayurvedic claims and indicate that Bacopa monniera can improve the performance of rats in various learning situations.

Pharmacological studies on coleonol, a hypotensive diterpene from Coleus forskohlii☆

Coleus spp. have been used in Aurvedic medicine for heart diseases, spasmodic pain, painful micturition and convulsions. The pharmacological properties of coleonol, a diterpene, isolated from Coleus forskohlii were investigated. Its predominant effect is to lower the blood pressure of anaesthetised cat and rat as well as of the spontaneously hypertensive rat due to relaxation of the vascular smooth muscle. In small doses it has a positive inotropic effect on isolated rabbit heart as well as on cat heart in vivo. Coleonol also exhibits nonspecific spasmolytic activity on smooth muscle of the gastrointestinal tract in various species but not on bronchial musculature of guinea pig. Large doses of coleonol have a depressant action on the central nervous system. These results provide the rationale for the use of this plant in Aurvedic medicine.

Ex vivo and in vivo investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in rats

Picroliv, the active constituent isolated from the plant Picrorhiza kurroa, was evaluated as a hepatoprotective agent against ethanol-induced hepatic injury in rats. Alcohol feeding (3.75 g/kg x45 days) produced 20-114% alteration in selected serum (AST, ALT and ALP) and liver markers (lipid, glycogen and protein). Further, it reduced the viability (44-48%) of isolated hepatocytes (ex vivo) as assessed by Trypan blue exclusion and rate of oxygen uptake. Its effect was also seen on specific alcohol-metabolizing enzymes (aldehyde dehydrogenase, 41%; acetaldehyde dehydrogenase, 52%) in rat hepatocytes. The levels of these enzymes were found to be reduced in the cells following alcohol intoxication. Ethyl alcohol also produced cholestasis (41-53%), as indicated by reduction in bile volume, bile salts and bile acids. Picroliv treatment (3-12 mg/kg p.o. x45 days) restored the altered parameters in a dose-dependent manner (36-100%).

Curative effect of picroliv on primary cultured rat hepatocytes against different hepatotoxins: an in vitro study

Picroliv, the standardized active principle from the plant Picrorhiza kurrooa showed significant curative activity in vitro in primary cultured rat hepatocytes against toxicity induced by thioacetamide (200 microg/mL), galactosamine (400 microg/mL), and carbon tetrachloride (3 microl/mL). Activity was assessed by determining the change in hepatocyte viability and rate of oxygen uptake and other biochemical parameters (GOT, GPT, and AP). The toxic agents alone produced a 40-62% inhibition of cell viability and a reduction of biochemical parameters after 24 h of incubation at 37 degrees C which (on removal of the toxic agents) was reversed after further incubation for 48 h. Incubation of damaged hepatocytes with picroliv exhibited a concentration- (1-100 microg/mL) dependent curative effect in restoring altered viability parameters. The results warrant the use of this in vitro system as an alternative for in vivo assessment of hepatoprotective activity of new agents.

Hepatoprotective Activity of Ricinus communis Leaves

AbstractRicinus communis (leaf extract) was evaluated for hepatoprotective, choleretic and anticholestatic activity. In a preliminary test with albino rats, an ethanol extract showed significant protection against galactosamine-induced hepatic damage. It also showed dose-dependent choleretic and anti cholestatic activity, and hepatoprotective activity as judged by hepatocytes isolated from paraceta mol-treated rats. On fractionation of the ethanol extract, maximum activity was localised in the butanol fraction. Subsequent chromatographic fractionation and testing in the galactosamine model led to the isolation of two active fractions which in turn yielded two pure compounds: ricinine and N-demethyl-ricinine. N-Demethyl-ricinine was found to be more active and it reversed the biochemical changes produced by galactosamine at a dose of 6 mg/kg x 7 days. It possessed marked choleretic activity and demonstrated an anticholestatic effect against paracetamol-induced cholestasis.

Evidence for the involvement of histamine in the regulation of blood-brain barrier permeability.

Role of histaminergic mechanisms in the regulation of blood-brain barrier (BBB) was assessed in dog. Histamine increased the entry of sodium fluorescein from the blood to the cerebrospinal fluid (CSF) in a dose-dependent manner. Histamine receptor antagonists, mepyramine (H1) and metiamide (H2) per se did not affect the entry of dye in the CSF. Mepyramine failed to affect the change induced by histamine whereas metiamide completely blocked the histamine-induced entry of sodium fluorescein in CSF. 2-Methyl histamine, a specific H1-agonist, did not affect the barrier permeability. However, 4-methyl histamine, a specific H2 receptor agonist significantly increased the permeability of BBB. This increase was blocked by metiamide. Forskolin, a stimulant of adenylate cyclase, also increased the entry of dye in the CSF which could be significantly blocked by metiamide. It is concluded that histamine increases the permeability of BBB by affecting H2-receptors linked to adenylate cyclase.

A PRIMATE MODEL OF ANXIETY

Pentylenetetrazol (PTZ; 30 mg/kg, i.m.) produced an acute anxiogenic effect on the behaviour of a social colony of rhesus monkeys acclimatized to laboratory conditions. The animals exhibited hypervigilance, aggressiveness, tachypnea, piloerection and frequent change of posture and also had raised plasma cortisol levels. These effects of PTZ were antagonized by benzodiazepines (diazepam; 1 mg/kg, i.v. and alprazolam; 0.05 mg/kg, p.o.). Non-benzodiazepine anxiolytic drug (buspirone; 10 mg/kg, p.o.) blocked the behavioural effects but not the rise in plasma cortisol concentration. On the other hand, pretreatment with hypnosedative (promethazine; 5 mg/kg, i.m.) or anticonvulsant (sodium valproate; 40 mg/kg, p.o.) agents did not attenuate the effects of PTZ indicating the specificity of its anxiogenic response. The model, thus, seems suitable for evaluation of potential anxiolytic agents.