Papers by Sapana Khandelwal
Journal of Current Pharma Research
Food and Chemical Toxicology, Jan 1, 2001
Six plant species (Cassia sophera, Chamaecrista nigricans, Mitragyna inermis, Ocimum americanum, ... more Six plant species (Cassia sophera, Chamaecrista nigricans, Mitragyna inermis, Ocimum americanum, Securidaca longepedunculata and Synedrella nodiflora) traditionally used in Ghana to control insect pests of stored grain and legumes were screened in the laboratory at three concentrations (0.5, 1 and 5%, w/w) against four common storage pests (Rhyzopertha dominica, Callosobruchus maculatus, Sitophilus zeamais and Prostephanus truncatus). All the plants showed some ability to control all or some of the test insect species. Levels of efficacy varied according to test concentration with the highest concentration tested providing the best control. The S. longepedunculata plant induced the highest percent mortality and was the best at reducing emergence of the F1 generation. The six plants were also incorporated into standard rat diet at two concentrations (1 and 5%, w/w) and fed to rats over a 6-week period to assess potential deleterious effects against vertebrates. None of the plants demonstrated any neurotoxicological or neurobehavioural effects to the rats over the course of the trial. However, S. longepedunculata and C. nigricans caused a significant reduction in rat growth rate when incorporated at 5% in the diet, induced cell hyperplasia in the liver, and reduced the mean weight of the liver and kidneys, compared to the control group of rats. Kidney pathology was affected only by the 5% concentration of S. longepedunculata which caused a reduced accumulation of α2μ-globulin. The implications of these results are discussed in the context of farmer usage of insecticidal plants for stored product protection.
Life Sciences, Jan 1, 1998
Mitragynine (MG), a major alkaloidal constituent extracted from the plant Mitragyna speciosa Kort... more Mitragynine (MG), a major alkaloidal constituent extracted from the plant Mitragyna speciosa Korth, is known to exert an opioid-like activity. Our previous study showed the involvement of opioid systems in the antinociceptive activity of MG in the tail-pinch and hot-plate tests in mice. In the present study, to clarify the opioid receptor subtypes involved in the antinociceptive action of MG, we investigated the effects of selective antagonists for μ-, δ- and κ- opioid receptors on antinociception caused by the intracerebroventricular (i.c.v.) injection of MG in the tail-pinch and hot-plate tests in mice. The coadministration of a selective μ-opioid antagonist, cyprodime (1–10 μg, i.c.v.) and the pretreatment with a selective μ1-opioid antagonist naloxonazine (1–3 μg, i.c.v.) significantly antagonized the antinociceptive activities of MG (10 μg, i.c.v.) and morphine (MOR, 3 μg, i.c.v.) in the tail-pinch and hot-plate tests. Naltrindole (1–5 ng, i.c.v.), a selective δ-opioid antagonist, also blocked the effects of MG (10 μg, i.c.v.) without affecting MOR (3 μg, i.c.v.) antinociception. Nor-binaltorphimine, a selective κ-opioid antagonist, significantly attenuated MG (10 μg, i.c.v.) antinociception in the tail-pinch test but not in the hot-plate test at the dose (1 μg, i.c.v.) that antagonized the antinociceptive effects of the selective κ-opioid agonist U50,488H in both tests, while it had no effect on MOR antinociception in either tests. These results suggest that antinociception caused by i.c.v. MG is dominantly mediated by μ- and δ-opioid receptor subtypes, and that the selectivity of MG for the supraspinal opioid receptor subtypes differs from that of MOR in mice.
Life Sciences, Jan 1, 1997
Effect of mitragynine, an indole alkaloid isolated from Thai medicinal plant kratom (Mitragyna sp... more Effect of mitragynine, an indole alkaloid isolated from Thai medicinal plant kratom (Mitragyna speciosa), on electrically stimulated contraction was studied in the guinea-pig ileum. Mitragynine (1 nM - 3 μM) inhibited the ileum contraction elicited by electrical stimulation, and its pD2 value was 6.91 ± 0.04 (n = 5). Morphine (1 nM − 1 μM) also inhibited the electrically stimulated contraction in a concentration-dependent manner (pD2 7.68 ± 0.11; n = 5). Mitragynine was 10 fold less potent than morphine. Mitragynine (3–10 μM) did not show any effect on the smooth muscle contraction induced by acetylcholine or histamine. Naloxone (10–300 nM) reversed the inhibitory effect of mitragynine on electrically stimulated contraction. Furthermore, naloxone showed a shift of concentration-response curve of mitragynine to the right. There was no significant difference in the affinity of naloxone (i.e. pA2) in the presence of mitragynine or morphine. Mitragynine (3–10 μM) inhibited the naloxone-precipitated withdrawal contraction following a brief (5 min) exposure of the ileum to morphine. Tetrodotoxin (1 μM) and atropine (1 μM) inhibited the withdrawal contraction. The present results suggest that mitragynine inhibits the electrically stimulated contraction of guinea-pig ileum through the opioid receptor.
Parasitology Research, Jan 1, 2002
In Mali, where malaria is endemic, plants are extensively used for treating periodic fevers and m... more In Mali, where malaria is endemic, plants are extensively used for treating periodic fevers and malaria. According to the advice of traditional medicine, plants are often mixed during the preparation of febrifugal decoctions. In previous studies, we demonstrated the potent in vitro antimalarial activity of extracts isolated from four plants commonly used in traditional remedies: Mitragyna inermis (Willd.) O. Kuntze, Rubiaceae, Nauclea latifolia (Sm.), Rubiaceae, Guiera senegalensis (Gmel.), Combretaceae, and Feretia apodanthera (Del.), Rubiaceae. In the present work, we evaluate the potent in vitro synergistic antimalarial interaction between these extracts, using standard isobologram analysis. Then, we evaluate their cytotoxicity on human monocytes and their mutagenic activity on an in vitro system of two beta-carboline alkaloids isolated from Guiera senegalensis (harman and tetrahydroharman). Three combinations demonstrate a strong, synergistic, inhibitory effect on in vitro plasmodial development and are devoid of cytotoxicity towards human cells. These results justify their use in association in traditional medicine. Moreover, tetrahydroharman, isolated from G. senegalensis, presents interesting antimalarial activity, no cytotoxicity and is not genotoxic in the Salmonella Ames test with and without metabolic activation.
Journal of Ethnopharmacology, Jan 1, 1988
Life Sciences, Jan 1, 2004
Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We p... more Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We previously reported the morphine-like action of mitragynine and its related compounds in the in vitro assays. In the present study, we investigated the opioid effects of 7-hydroxymitragynine, which is isolated as its novel constituent, on contraction of isolated ileum, binding of the specific ligands to opioid receptors and nociceptive stimuli in mice. In guinea-pig ileum, 7-hydroxymitragynine inhibited electrically induced contraction through the opioid receptors. Receptor-binding assays revealed that 7-hydroxymitragynine has a higher affinity for μ-opioid receptors relative to the other opioid receptors. Administration of 7-hydroxymitragynine (2.5–10 mg/kg, s.c.) induced dose-dependent antinociceptive effects in tail-flick and hot-plate tests in mice. Its effect was more potent than that of morphine in both tests. When orally administered, 7-hydroxymitragynine (5–10 mg/kg) showed potent antinociceptive activities in tail-flick and hot-plate tests. In contrast, only weak antinociception was observed in the case of oral administration of morphine at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid agonist that is structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.
European Journal of Pharmacology, Jan 1, 1996
Mitragynine is a major alkaloidal constituent of young leaves of Mitragyna speciosa Korth, that i... more Mitragynine is a major alkaloidal constituent of young leaves of Mitragyna speciosa Korth, that is known to exhibit narcotic-like activity. In this study, we investigated the roles of central monoaminergic systems in the antinociceptive action of mitragynine by means of the tail-pinch and hot-plate tests in mice. Mitragynine (1.0–10 μg) injected i.c.v. exerted a dose-dependent antinociceptive activity in both tests. The activity of mitragynine (10 μg, i.c.v.) in the tail-pinch test was antagonized by reserpine, 6-hydroxydopamine plus nomifensine, and p-chlorophenylalanine treatment, whereas the antinociceptive activity of morphine (3 μg) given i.c.v. in this test was attenuated by 6-hydroxydopamine plus nomifensine but not by p-chlorophenylalanine treatment. Moreover, the activity of i.c.v. mitragynine was also antagonized by the α2-adrenoceptor antagonist, idazoxan (10 μg), and cyproheptadine (1 μg) administered intrathecally (i.t.). On the other hand, the antinociceptive action of i.c.v. mitragynine (10 μg) in the hot-plate test was abolished by reserpine and 6-hydroxydopamine plus nomifensine, but not by p-chlorophenylalanine treatment. This action was also antagonized by i.t. injection of idazoxan (10 μg). These results suggest that both descending noradrenergic and serotonergic systems are involved in the antinociceptive activity of supraspinally administered mitragynine on the mechanical noxious stimulation, while the descending noradrenergic system predominantly contributes to the effect of supraspinal mitragynine on the thermal noxious stimulation. The mechanisms underlying the suppressive action of mitragynine on the nociceptive response may differ from those of morphine in mice.
Uploads
Papers by Sapana Khandelwal