neoline and benzoylmesaconine

Fuzi, the lateral roots of Aconitum carmichaelii Debx, plays an irreplaceable role in treating Yang deficiency and cold coagulation syndromes. However, Fuzi has a narrow margin of safety since its pharmacological constituents, Aconitum alkaloids, have potential cardiotoxicity and neurotoxicity. The current quality markers (Q-markers) for the control of Fuzi's efficacy and toxicity are 3 monoester-diterpenoid alkaloids, namely, benzoylaconine (BAC), benzoylhypaconine and benzoylmesaconine (BMA) and 3 diester-diterpenoid alkaloids, namely, aconitine (AC), hypaconitine and mesaconitine (MA). However, mounting evidence indicates that the current 6 Q-markers may not be efficacy- or toxicity-specific enough for Fuzi.. The aim of this study was to explore and evaluate efficacy- or toxicity-specific potential quality markers (PQ-markers) of Fuzi.. PQ-markers were explored by analyzing 30 medicinal samples and alkaloids exposed in mouse. Pharmacokinetics of PQ-markers on C57BL/6J mice were determined. Anti-inflammatory effects of PQ-markers were evaluated by λ-carrageenan-induced paw edema model and lipopolysaccharide-induced RAW264.7 cell inflammatory model, while analgesic effects were assessed by acetic acid-induced pain model and Hargreaves test. Cardiotoxicity and neurotoxicity of PQ-markers were assessed by histological and biochemical analyses, while acute toxicity was evaluated by modified Kirschner method.. Seven PQ-markers of Fuzi were found after in vitro and in vivo explorations. Among them, NE, FE and SE were found to be more efficacy-specific than BMA, and 10-OH MA was as toxicity-specific as MA.

Topics: Aconitine; Aconitum; Alkaloids; Analgesics; Animals; Anti-Inflammatory Agents; Chromatography, High Pressure Liquid; Diterpenes; Drugs, Chinese Herbal; Mice; Mice, Inbred C57BL; Plant Roots

Processed aconite root (PA), the root of Aconitum carmichaeli (Ranunculaceae), is a crude drug used in traditional Chinese or Japanese kampo medicine to treat pain associated with coldness. In our previous study, PA and its active ingredient, neoline, alleviated oxaliplatin-induced peripheral neuropathy in mice.. The present study investigated the effects of PA on a murine peripheral neuropathy model induced by intraperitoneal injection of paclitaxel and partial ligation of the sciatic nerve (Seltzer model), and identified its active ingredients.. PA powder (1 g/kg/day) was orally administered, and either neoline or benzoylmesaconine (10 mg/kg/day) was subcutaneously injected into the murine model. Mechanical hyperalgesia was evaluated via the von Frey filament method. PA extract was orally administered to rats; blood samples were chronologically collected, and the plasma concentrations of Aconitum alkaloids were measured. The contents of Aconitum alkaloids in commercial PA products were also measured.. PA extract and neoline significantly attenuated the mechanical hyperalgesia induced by either paclitaxel or partial ligation of the sciatic nerve in mice. In the plasma samples of rats treated with PA extract, higher concentrations of benzoylmesaconine and neoline were apparent among Aconitum alkaloids. The contents of benzoylmesaconine and neoline varied among PA products with different processing procedures. Subcutaneous injection of benzoylmesaconine did not attenuate the hyperalgesia induced by each paclitaxel, partial ligation of the sciatic nerve, or oxaliplatin in mice.. The present results indicate that PA and its active ingredient, neoline, are promising agents for the alleviation of neuropathic pain. Neoline can be used as a marker compound to determine the quality of the PA products for the treatment of neuropathic pain.

Topics: Aconitine; Aconitum; Analgesics; Animals; Antineoplastic Agents, Phytogenic; Hyperalgesia; Male; Mice; Neuralgia; Paclitaxel; Peripheral Nerve Injuries; Plant Roots; Rats, Wistar; Sciatic Nerve