Antinociceptive Effect of Tephrosia sinapou Extract in the Acetic Acid, Phenyl-p-benzoquinone, Formalin, and Complete Freund's Adjuvant Models of Overt Pain-Like Behavior in Mice.

Tephrosia toxicaria, which is currently known as Tephrosia sinapou (Buc'hoz) A. Chev. (Fabaceae), is a source of compounds such as flavonoids. T. sinapou has been used in Amazonian countries traditional medicine to alleviate pain and inflammation. The purpose of this study was to evaluate the analgesic effects of T. sinapou ethyl acetate extract in overt pain-like behavior models in mice by using writhing response and flinching/licking tests. We demonstrated in this study that T. sinapou extract inhibited, in a dose (1-100 mg/kg) dependent manner, acetic acid- and phenyl-p-benzoquinone- (PBQ-) induced writhing response. Furthermore, it was active via intraperitoneal, subcutaneous, and peroral routes of administration. T. sinapou extract also inhibited formalin- and complete Freund's adjuvant- (CFA-) induced flinching/licking at 100 mg/kg dose. In conclusion, these findings demonstrate that T. sinapou ethyl acetate extract reduces inflammatory pain in the acetic acid, PBQ, formalin, and CFA models of overt pain-like behavior. Therefore, the potential of analgesic activity of T. sinapou indicates that it deserves further investigation.

Tephrosia sinapou ethyl acetate extract inhibits inflammatory pain in mice: opioid receptor dependent inhibition of TNFα and IL-1ß production.

UNLABELLED: CONTEXT. Tephrosia toxicaria is currently known as Tephrosia sinapou (Buc'hoz) A. Chev. (Fabaceae) and is a source of compounds such as flavonoids that inhibit inflammatory pain. OBJECTIVE: To investigate the analgesic effect and mechanisms of the ethyl acetate extract of T. sinapou in inflammatory pain in mice. MATERIALS AND METHODS: Behavioral responses were evaluated using mechanical (1-24 h) and thermal hyperalgesia (0.5-5 h), writhing response (20 min) and rota-rod (1-5 h) tests. Neutrophil recruitment (myeloperoxidase activity), cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1ß), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels were determined by colorimetric assays. Pharmacological treatments were opioid receptor antagonist (naloxone, 0.1-1 mg/kg) and control opioid (morphine, 5 mg/kg). Inflammatory stimuli were carrageenin (100 µg/paw), complete Freund's adjuvant (CFA, 10 µl/paw), prostaglandin E2 (PGE2, 100 ng/paw) and acetic acid (0.8%). RESULTS: The intraperitoneal pre-treatment with extract inhibited in a dose-dependent (30-300 mg/kg) dependent manner the mechanical hyperalgesia induced by carrageenin (up to 93% inhibition). The post-treatment (100 mg/kg) inhibited CFA-induced hyperalgesia (up to 63% inhibition). Naloxone (1 mg/kg) prevented the inhibitory effect of the extract over carrageenin-induced mechanical (100%) and thermal (100%) hyperalgesia, neutrophil recruitment (52%) and TNFα (63%) and IL-1ß (98%) production, thermal threshold in naïve mice (99%), PGE2-induced mechanical hyperalgesia (88%) and acetic acid-induced writhing response (49%). There was no significant alteration in the rota-rod test, and AST and ALT serum levels by extract treatment. Discussion and conclusion. Tephrosia sinapou ethyl acetate extract reduces inflammatory pain by activating an opioid receptor-dependent mechanism.

Tephrosia sinapou extract reduces inflammatory leukocyte recruitment in mice: effect on oxidative stress, nitric oxide and cytokine production

Tephrosia toxicaria (Sw.) Pers., which is currently known as T. sinapou (Buc'hoz) A. Chev., Fabaceae, is a source of compounds such as flavonoids, however, few studies addressed the anti-inflammatory and antioxidant effects of T. sinapou. Therefore, we evaluated the antioxidant mechanisms of the T. sinapou ethyl acetate extract in vitro, and whether the extract affects leukocyte recruitment in four models of inflammation and the involvement of nitric oxide and cytokines in its mechanism. In vitro, it was observed that the extract presented hydrogen donating ability to 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH), 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS+), and also efficiently inhibited iron-dependent and independent lipid peroxidation and iron chelation assays. In vivo, it inhibited the recruitment of total leukocytes and neutrophil induced by carrageenin, zymosan, glycogen and lipopolysaccharide in the peritoneal cavity of mice. Two mechanisms were detected: 1) T. sinapou effect on leukocyte recruitment depends on nitric oxide since was dose-dependently inhibited by treatment with L-NAME (nitric oxide synthase inhibitor), and 2) the extract also inhibited the production of crucial cytokines for the leukocyte recruitment; tumor necrosis factor α and interleukin-1β. Concluding, T. sinapou ethyl acetate extract reduces oxidative stress in vitro, and inflammatory leukocyte recruitment by a mechanism related to inhibition of cytokine production, and in a nitric oxide dependent manner in vivo.

New spirorotenoids from Tephrosia candida.

The ethyl acetate extract of roots of Tephrosia candida afforded three new spirorotenoids belonging to a new class of spirocompounds, named tephrospirolactone, tephrospiroketone I, and tephrospiroketone II. The structures of these compounds were determined mainly based on spectral analysis. The only known spirorotenoid described in the literature is amorphispironone, isolated from Amorpha fruticosa.