Khalid Hussain Janbaz

Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents

Rutin, a well-known flavonoid was investigated for its possible protective effect against paracetamol- and CCl(4)-induced hepatic damage. Paracetamol produced 100% mortality at the dose of 1 g/kg in mice while pre-treatment of animals with rutin (20 mg/kg) reduced the death rate to 40%. Oral administration of a sub-lethal dose of paracetamol (640 mg/kg) produced liver damage in rats as manifested by the rise in serum level of transaminases (AST and ALT). Pre-treatment of rats with rutin (20 mg/kg) prevented the paracetamol-induced rise in serum enzymes. The hepatotoxic dose of CCl(4) (1.5 ml/kg; orally) also raised the serum AST and ALT levels. The same dose of rutin (20 mg/kg) was able to prevent the CCl(4)-induced rise in serum enzymes. Rutin also prevented the CCl(4)-induced prolongation in pentobarbital sleeping time confirming its hepatoprotectivity. These results indicate that rutin possesses hepatoprotective activity and the presence of this compound in Artemisia scoparia may explain the folkloric use of the plant in liver damage.

Preventive and curative effects of Artemisia absinthium on acetaminophen and CCl4-induced hepatotoxicity

1. Effect of aqueous-methanolic extract of Artemisia absinthium (Compositae) was investigated against acetaminophen- and CCl4-induced hepatic damage. 2. Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice while pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to 20%. 3. Pretreatment of rats with plant extract (500 mg/kg, orally twice daily for two days) prevented (P < 0.01) the acetaminophen (640 mg/kg) as well as CCl4 (1.5 ml/kg)-induced rise in serum transaminases (GOT and GPT). 4. Post-treatment with three successive doses of extract (500 mg/kg, 6 hr) restricted the hepatic damage induced by acetaminophen (P < 0.01) but CCl4-induced hepatotoxicity was not altered (P > 0.05). 5. Plant extract (500 mg/kg) caused significant prolongation (P < 0.05) in pentobarbital (75 mg/kg)-induced sleep as well as increased strychnine-induced lethality in mice suggestive of inhibitory effect on microsomal drug metabolizing enzymes (MDME). 6. These results indicate that the crude extract of Artemisia absinthium exhibits hepatoprotective action partly through MDME inhibitory action and validates the traditional use of plant in hepatic damage.

STUDIES ON PREVENTIVE AND CURATIVE EFFECTS OF BERBERINE ON CHEMICAL-INDUCED HEPATOTOXICITY IN RODENTS

Berberis aristata is an edible plant employed in the South Asian Traditional Medicine, particularly its fruits being used as a tonic remedy for liver and heart. In this investigation, berberine, a known compound from this plant, was studied for its possible antihepatotoxic action in rats. Pretreatment of animals with berberine (4 mg/kg; orally twice daily for 2 days) prevented the acetaminophen- or CCl4-induced rise in serum levels of alkaline phosphatase (ALP) and aminotransaminases (AST and ALT), suggestive of hepatoprotection. Post-treatment with three successive oral doses of berberine (4 mg/kg every 6 h) reduced the hepatic damage induced by acetaminophen, while CCl4-induced hepatotoxicity was not modified, suggesting a selective curative effect against acetaminophen. Pretreatment of animals with a single oral dose of berberine (4 mg/kg) induced prolongation of the pentobarbital (60 mg/kg, i.p.)-induced sleeping time as well as increased strychnine (0.3 mg/kg; i.p.)-induced toxicity, suggestive of inhibitory effect on microsomal drug metabolizing enzymes, cytochrome P450s (CYPs).

Studies on antihypertensive and antispasmodic activities of methanol extract of Acacia nilotica pods

A methanol extract of Acacia nilotica pods (AN) caused a dose‐dependent (3–30 mg/kg) fall in arterial blood pressure. Treatment of animals with atropine abolished the vasodilator response of acetylcholine (ACh), whereas the antihypertensive effect of the plant extract remained unaltered. Phentolamine (an α‐adrenergic blocker) abolished the vasoconstrictor effect of norepinephrine (NE), whereas pretreatment of the animal with AN, did not modify the NE response. These results indicate that the antihypertensive effect of plant extract is independent of muscarinic receptor stimulation or adrenoceptor blockade. In the in vitro studies, AN produced a dose‐dependent (0.3–3.0 mg/mL) inhibitory effect on force and rate of spontaneous contractions in guinea‐pig paired atria. Similarly, it inhibited the spontaneous contraction of rabbit jejunum in a concentration‐dependent (0.1–3.0 mg/mL) manner. AN also inhibited K+‐induced contractions in rabbit jejunum at a similar concentration range, which suggests that the antispasmodic action of AN is mediated through calcium channel blockade, and this may also be responsible for the blood pressure lowering effect of AN, observed in the in vivo studies. Copyright

Evaluation of the protective potential of Artemisia maritima extract on acetaminophen- and CCl4-induced liver damage

The hepatoprotective activity of the aqueous-methanolic extract of Artemisia maritima was investigated against acetaminophen (paracetamol, 4-hydroxy acetanilide)- and carbon tetrachloride (CCl4)-induced hepatic damage. Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice, while pretreatment of animals with the plant extract (500 mg/kg) reduced the death rate to 20%. Acetaminophen at the dose of 640 mg/kg produced liver damage in rats as manifested by the significant (P < 0.001) rise in serum levels of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 1529 +/- 172 I.U./l and 904 +/- 116 I.U./l (n = 10), respectively, compared to respective control values of 87 +/- 12 I.U./l and 31 +/- 5 I.U./l. Pretreatment of rats with the plant extract (500 mg/kg) lowered significantly (P < 0.001) the respective serum GOT and GPT levels to 112 +/- 10 I.U./l and 47 +/- 11 I.U./l. Similarly, a hepatotoxic dose of CCl4 (1.5 ml/kg, orally) raised significantly (P < 0.01) the serum GOT and GPT levels to 463 +/- 122 I.U./l and 366 +/- 58 I.U./l (n = 10), respectively, compared to respective control values of 92 +/- 18 I.U./l and 35 +/- 9 I.U./l. The same dose of plant extract (500 mg/kg) was able to prevent significantly (P < 0.01) the CCl4-induced rise in serum transaminases and the estimated values of GOT and GPT were 105 +/- 29 I.U./l and 53 +/- 17 I.U./l, respectively. Moreover, it prevented CCl4-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity and validates the traditional use of this plant against liver damage.

Novel drugs from marine microorganisms

Marine microorganisms have expected mounting consideration on the basis of bioactive metabolites and propose an exclusive prospect to both enhance the amount of aquatic natural foodstuffs in clinical trials as well as speed up their progress. This review focuses particularly on those molecules, originated from marine microorganisms, presently in the medical pipeline that have been recognized or highly expected to be identified based on growing incidental evidence. Particularly karlotoxin class compounds, isolated from dinoflagellate Karlodinium veneficum, offer chances to create new molecules for control of cancer and high serum cholesterol levels.

Selective protective effect of an extract from Fumaria parviflora on paracetamol-induced hepatotoxicity

1. The hepatoprotective activity of an aqueous-methanolic extract of Fumaria parviflora was investigated against paracetamol- and CCI4-induced hepatic damage. 2. Paracetamol (1 g/kg; orally) produced 100% mortality in mice; pretreatment of animals with the plant extract (500 mg/kg; orally) reduced the death rate to 50%. 3. Pretreatment of rats with plant extract (500 mg/kg, orally twice daily for 2 days) prevented (P < 0.001) the paracetamol (640 mg/kg)-induced rise in serum enzymes alkaline phosphatase (ALP) and transaminases (GOT and GPT), whereas the same dose of the extract was unable to prevent (P > 0.05) the CCI4-induced rise in serum enzyme levels. 4. Posttreatment with 3 successive doses of the extract (500 mg/kg, 6 hourly) also restricted the paracetamol-induced hepatic damage. 5. The plant extract (500 mg/kg; orally) caused significant prolongation in pentobarbital (75 mg/ kg)-induced sleep as well as increased strychnine-induced lethality in mice (P < 0.05), suggestive of an inhibitory effect on microsomal drug metabolizing enzymes (MDME). 6. It is conceivable therefore, that Fumaria parviflora extract exhibits a selective protective effect against paracetamol-induced hepatotoxicity, probably mediated through MDME inhibition.

Studies on protective effect of Cyperus Scariosus extract on acetaminophen and CCl4-induced hepatotoxicity

1. The hepatoprotective activity of aqueous-methanolic extract of Cyperus scariosus (Cyperaceae) was investigated against acetaminophen and CCl4-induced hepatic damage. 2. Acetaminophen produced 100% mortality at a dose of 1 g/kg in mice while pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to 30%. 3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 430 +/- 68, 867 +/- 305 and 732 +/- 212 IU/l (n = 10) respectively, compared to respective control values of 202 +/- 36, 59 +/- 14 and 38 +/- 7. 4. Pretreatment of rats with plant extract (500 mg/kg) significantly lowered (P < 0.05) the respective serum ALP; GOT and GPT levels to 192 +/- 31, 63 +/- 9 and 35 +/- 8. 5. The hepatotoxic dose of CCl4 (1.5 ml/kg; orally) raised serum ALP, GOT and GPT levels to 328 +/- 30, 493 +/- 102 and 357 +/- 109 IU/l (n = 10) respectively, compared to respective control values of 177 +/- 21, 106 +/- 15 and 47 +/- 12. 6. The same dose of plant extract (500 mg/kg) was able to significantly prevent (P < 0.05) CCl4-induced rise in serum enzymes and the estimated values of ALP, GOT and GPT were 220 +/- 30, 207 +/- 95 and 75 +/- 38, respectively. 7. The plant extract also prevented CCl4-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypotensive and spasmolytic activities of crude extract ofCyperus scariosus

Intravenous administration of hydro-methanolic extract ofCyperus scarious (3–10 mg/kg) produced hypotensive and bradycardiac effects. These effects remained unaltered in atropinized animals indicating that cardiovascular effects of the plant extract are not mediated through activation of muscarinic receptors. In thein vitro studies, it suppressed the spontaneous contractions of guinea-pig paired atria, rat uterus and rabbit jejunum in a concentration-dependent (0.1–1 mg/ml) manner. It also inhibited histamine or acetylcholine-induced contractions of guinea-pig ileum indicating non-specific spasmolytic action. In rabbit aorta, it inhibited norepinephrine (10 μM) as well as K+ (80 mM)-induced contractions at similar concentrations (0.1–1mg/ml). These data indicate thatCyperus scariosus contains Ca2+ channel blocker-like constituent(s) which may explain hypotensive effect observedin vivo and the general spasmolytic activity of plant may explain its folkloric use in diarrhoea.

Protective effect of Artemisia scoparia extract against acetaminophen-induced hepatotoxicity

1. Hepatoprotective activity of hydro-methanolic extract of Artemisia scoparia (Compositae) was investigated against acetaminophen-induced hepatic damage. 2. Acetaminophen at a dose of 1 g/kg produced 100% mortality in mice while pretreatment of animals with plant extract (150 mg/kg) reduced the death rate to 20%. 3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of GOT and GPT to 1528 +/- 310 and 904 +/- 261 IU/l (n = 10) respectively, compared to respective control values of 80 +/- 11 and 38 +/- 09. 4. Pretreatment of rats with plant extract (150 mg/kg) lowered significantly the respective serum GOT and GPT levels to 85 +/- 11 and 23 +/- 06. 5. These results indicate that Artemisia scoparia contains hepatoprotective constituents and this study rationalizes the traditional use of this plant in hepatobiliary disorders.