Wantana Reanmongkol

Antinociceptive activity of the methanolic extract of Kaempferia galanga Linn. in experimental animals.

Kaempferia galanga Linn. (Zingiberaceae) presents many chemical constituents of the volatile oil extracted from the rhizome. The rhizome of Kaempferia galanga is used by people in many regions for relieving toothache, abdominal pain, muscular swelling and rheumatism. In this study we investigated the antinociceptive activity in mice and rats using acetic acid-induced writhing, formalin, hot plate and tail-flick tests. The extract at test doses of 50, 100 and 200 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. This activity was dose- and time-dependent. The extract administered at 200 mg/kg, p.o. had a stronger antinociceptive effect than aspirin (100 mg/kg, p.o.) but less than morphine (5 mg/kg, s.c.). Naloxone (2 mg/kg, i.p.) abolished the antinociceptive action of both morphine (5 mg/kg, s.c.) and the extract (200 mg/kg, p.o.) in a similar manner. In conclusion, the methanol extract of Kaempferia galanga markedly demonstrated the antinociceptive action in experimental animals. The antinociceptive mechanisms appear to be both peripherally and centrally mediated actions and the opioid receptors are probably involved. Therefore, our studies support the use in traditional medicine of Kaempferia galanga against pain caused by various disorders.

Topical anti-inflammatory and analgesic activities of standardized pomegranate rind extract in comparison with its marker compound ellagic acid in vivo

ETHNOPHARMACOLOGICAL RELEVANCE In Chinese traditional medicine, the peels of Punica granatum L. have been used to treat traumatic hemorrhage, burn, and ulcers. AIMS OF THE STUDY This study aimed to assess the topical anti-inflammatory and analgesic activities of a standardized pomegranate rind extract (SPRE) of which ellagic acid (EA) was the major antioxidant constituent and the marker compound. MATERIAL AND METHODS The topical anti-inflammatory effects of SPRE were evaluated against acute models (croton oil-induced mouse ear edema and carrageenan-induced rat paw edema) and chronic model (complete Freunds adjuvant (CFA)-induced polyarthritis). The topical analgesic activities of SPRE were investigated in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test. All studies of SPRE were carried out in parallel with its marker compound EA. RESULTS SPRE (5%, 2.5%, and 1%, w/w) and the equivalent EA (0.65%, 0.325%, and 0.13%, w/w) dose-dependently reduced the croton oil-induced mouse ear edema with a maximal inhibition of 86.30% and 80.82%, respectively. SPRE dose-dependently attenuated the inflammatory responses in the carrageenan-induced rat paw edema and in the CFA-induced polyarthritis but the equivalent EA were effective only at the doses of 0.65% and 0.325%. Both SPRE (5%) and EA (0.65%) showed significant topical analgesic activities in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test. CONCLUSIONS SPRE was more active as an anti-inflammatory agent than EA. The anti-inflammatory and analgesic effects of SPRE were achieved through inhibiting the leukocyte infiltration and modulating the pro-inflammatory cytokines IL-β and TNF-α. These results clearly demonstrated that SPRE is a promising phytomedicine that could find use in the treatment of inflammatory diseases.

Uterine relaxant effects of Curcuma aeruginosa Roxb. rhizome extracts.

The effects and plausible mechanism of action of Curcuma aeruginosa Roxb. (Zingiberaceae) rhizome chloroform and methanol extracts on the uterine contraction were investigated using isolated uterus strips from estrogen primed rats. The contractile responses were recorded isometrically with a Grass FT03 force transducer connected to a MacLab system. The experiments were carried out on both nonstimulated, agonist- and KCl-stimulated uteri. In the nonstimulated uterus, the two extracts (10-400 microg/ml) had no significant effect. In contrast, in the stimulated uterus, the chloroform and methanol extracts exerted concentration-dependent inhibition of the contractions induced by oxytocin (1 mU/ml), prostaglandin F2alpha (PGF2alpha, 0.5 microg/ml), ACh (3x10(-6) M) and KCl (40 mM) with the IC50 (inhibition of force) of 31.4, 58.59, 56.21 and 29.28 microg/ml; and 57.79, 69.3, 223.8 and 69.19 microg/ml, respectively. Verapamil, the reference L-type calcium channel blocker, exhibited a similar pattern of inhibition with the IC50 of 0.03, 0.25, 0.35 and 0.04 microg/ml. The IC50 of diclofenac against a PGF2alpha-induced contraction was 31.36 microg/ml. It is known that the contraction induced by agonists and KCl is mainly due to calcium influx through the voltage-gated L-type calcium channels opened indirectly or directly by agonist-receptor activation and KCl. Thus, it is speculated that the two plant extracts might inhibit uterine contraction by interrupting the influx of Ca2+ probably through voltage-gated L-type calcium channels. This possibility was further substantiated by the ability of the extracts to shift the CaCl2-contraction curves to the right. As the methanol extract also reduced the contraction of oxytocin in Ca2+-free EDTA solution; thus, it is suggested that part of its action may be involved with an intracellular mechanism. The effect of the two extracts did not involve the activation of beta2-adrenoceptors since their effects were unaffected by propranolol. Based on the inhibitory effect of the extracts on the oxytocin-induced contraction, it is concluded that the extracts might be useful as tocolytic agents for the prevention of preterm labor. Their effects on the inhibition of PGF2alpha-induced contractions also seem useful for the treatment of dysmenorrhea. There are reports by others that the plant rhizome contains beta-pinene and sesquiterpenes. In addition, there is evidence that these compounds possess spasmolytic effects in the rat intestine and uterus. Therefore, the uterine relaxant effect of the plant extracts could be due to beta-pinene and some sesquiterpene lactones contents. The methanol extract is less potent than the chloroform extract, and this might be due to the lower amount of terpene compounds or different compounds may involve in this action.

Anti-allergic and antioxidative activities of some compounds from Thai medicinal plants

Evaluation of the anti-allergic and antioxidative activities of compounds from Thai medicinal plants demonstrated that lawsone methyl ether significantly exhibited the inhibitory effect on degranulation in RBL-2H3 cells with an EC50 of 26.71 µM, while quercetin, a standard control, had an EC50 of 10.02 µM. Other compounds from Thai medicinal plants including lucidin-ω-methyl ether, bergenin, homorapanone, strictosidinic acid and barakol, had no effect on the degranulation assay. In a DPPH radical scavenging assay, strictosidinic acid and barakol were more potent than the positive control, BHT. The EC50 values of strictosidinic acid and barakol were 27.68 and 39.62 µM, respectively. Other tested compounds, including lawsone methyl ether, bergenin, homorapanone and lucidin-ω-methyl ether, had weak antioxidative activities or no activity. In a nitrite assay, only lawsone methyl ether reduced nitrite production with an EC50 of 10.27 µM in RAW 264.7 cells. In conclusion, lawsone methyl ether suppresses degranulation in RBL-2H3 cells and reduces nitrite production in RAW 264.7 cells whereas strictosidinic acid and barakol have an antiradical action against DPPH.

Evaluation of Chemical Stability and Skin Irritation of Lawsone Methyl Ether in Oral Base

An antifungal naphthoquinone, lawsone methyl ether, was semisynthesized by methylation of lawsone. It exhibited low acute toxicity with a LD 50 of 70.7 mg/kg upon intraperitoneal administration in mice. An oral preparation of 0.5 % lawsone methyl ether in sodium carboxymethyl cellulose oral base appeared to be stable under a heating-cooling cycle test. Lawsone methyl ether in oral base did not cause any skin irritation under a primary skin irritation test and a cumulative skin irritation test. In contrast, the solution of lawsone methyl ether, potassium salt, produced erythema with some papulosquamous in the cumulative skin irritation test.

Topical Anti‐inflammatory Potential of Standardized Pomegranate Rind Extract and Ellagic Acid in Contact Dermatitis

The present study evaluated the topical anti‐inflammatory potential of a standardized pomegranate rind extracts (SPRE) in parallel with its marker compound ellagic acid (EA, 13% w/w) against a mouse model of contact dermatitis. In the phenol‐induced mouse ear edema, topical application of SPRE (5, 2.5, and 1 mg/ear) and EA (0.65, 0.325, and 0.13 mg/ear, equivalent to its content in SPRE) dose‐dependently reduced the ear edema with the maximal inhibition of 79.12% and 73.63%, respectively. Triamcinolone (0.1 mg/ear) and diclofenac (1 mg/ear) as reference drugs inhibited the edema by 73.63% and 37.91%. Myeloperoxidase (MPO) activity in the mouse ear was also decreased by SPRE and EA up to 69.68% and 68.79%, respectively. Triamcinolone and diclofenac decreased the MPO activity by 76.66% and 80.14% similarly. The results indicated that topical application of SPRE and EA is promising for use in the treatment of inflammatory skin disorders. Copyright

Analgesic and antipyretic activities of n-butanol alkaloids extracted from the stem bark hunteria zeylanica and its major constituent, strictosidinic acid, in mice

The pharmacological activities of the n -butanol alkaloids extracted from the stem bark of Hunteria zeylanica (Retz) Gardn. ex Thw. ( H. zeylanica ) and its major constituent, strictosidinic acid, on nociceptive response using writhing and hot plate tests, the antipyretic activity in yeast-induced fever, pentobarbital-induced sleep, and locomotor activity were examined in mice. Oral administration of H. zeylanica extract at 200 mg/kg significantly decreased the number of contortions and stretchings induced by acetic acid but not heat-induced pain. Strictosidinic acid (5–20 mg/kg, p.o.) also produced a similar effect but less pronounced than the extract. The antipyretic effect of strictosidinic acid (5–20 mg/kg, p.o.) was stronger than that of the extract (100–200 mg/kg, p.o.). The H. zeylanica extract dose-dependently (50–200 mg/kg, p.o.) prolonged the duration of pen-tobarbital-induced sleep but had no sign ificant effect on locomotor activity. No effect of strictosidinic acid was noted on both pentobarbital-induced sleep and locomotor activity. These results suggest that the H. zeylanica extract possesses peripheral analgesic and mild antipyretic effects and its major constituent, strictosidinic acid, exerts a similar analgesic effect with marked antipyretic activity.

Incidence and risk for neutropenia/agranulocytosis among clozapine users: A retrospective cohort study.

Abstract Objective. To estimate the incidence and the risk of neutropenia or agranulocytosis (the outcome) associated with clozapine use (the exposure), and to identify risk factors. Methods. All data were derived from the computerized hospital database. Adult psychiatric patients were identified, and 95 incident clozapine users and 884 non-clozapine users were included. Cox proportional hazards regression was used to estimate the hazards ratio (HR) of developing the outcome after clozapine use adjusted for confounders. The interaction between clozapine and valproic acid was assessed a posteriori. Results. Throughout the 24-month follow-up, the incidence of neutropenia was 6.3% in the clozapine group and 5.8% in the non-clozapine group. One agranulocytosis was found in the non-clozapine group. The HR (95% CI) for neutropenia were: clozapine 1.33 (0.54–3.25) and age . 45 years 2.99 (1.63–5.48). Lithium, as an independent protective factor, reduced the risk for neutropenia by 85% compared with patients who did not receive lithium, HR 0.15 (95% CI 0.02–1.09). Valproic acid might potentiate the clozapine-associated neutropenia (HR 5.10, 95% CI 0.70–37.12). Conclusion. Clozapine might slightly increase the risk of neutropenia in psychiatric patients. Concerning clozapine-associated neutropenia, older patients are at increased risk and use of valproic acid concurrently with clozapine should be avoided.

Physicochemical properties, in vitro release and in vivo evaluation of tramadol hydrochloride rectal suppository and rectal gel

Abstract Background: Tramadol is a centrally acting analgesic drug. Rectal administration of tramadol is useful in the treatment of post-operative pain or malignant pain in cases where it cannot be administered orally. In Thailand, tramadol is available only as a capsule for oral use and as a solution for injection. Objective: Develop tramadol hydrochloride rectal suppositories and rectal gel preparations. Methods: Tramadol rectal suppository and rectal gel were prepared. Physicochemical properties (viscosity, gel strength, mucoadhesive force) and the in vitro release of tramadol hydrochloride were investigated from different bases (Witepsol H15, polyethylene glycol, poloxamer, and hydroxyethylcellulose). The analgesic activity of rectal tramadol hydrochloride using the hot plate test was evaluated in rats. Results: Tramadol hydrochloride rectal gel using poloxamer was more mucoadhesive to the rectal mucous membrane than was the gel with the hydroxyethylcellulose base. Tramadol hydrochloride was released rapidly in vitro from both the Witepsol H15 and polyethylene glycol bases. It was completely released from the polyethylene glycol suppository base within 15 minutes. The amount of tramadol hydrochloride release from the Witepsol H15 suppository base was about 93% at 120 minutes. When using poloxamer or hydroxyethylcellulose as a rectal base, tramadol hydrochloride was released from both bases rapidly and completely released within 15 minutes. Administration of a tramadol hydrochloride suppository in rats exhibited a more pronounced analgesic effect with the polyethylene glycol base than with the Witepsol H15-based suppositories. The rectal gel had a less pronounced analgesic effect when made with the hydroxyethylcellulose base than with the poloxamer base. Conclusion: Tramadol hydrochloride suppositories and rectal gels with different bases showed rapid and almost complete drug release from the bases, prolonging the latency of a nociceptive response in in vivo experiments.