Evaluation of pharmacokinetics and blood-brain barrier permeability of mitragynine using in vivo microdialysis technique

A microdialysis system coupled with a sensitive ultra-fast liquid chromatography–mass spectrometry (UFLC-MS) method was developed for the pharmacokinetic analysis of mitragynine in rat blood and striatum. Mitragynine is an active alkaloid of Mitragyna speciosa and has been proposed to be used for opioid withdrawal therapy. In this study, chromatographic separation was performed in a gradient elution mode with 0.1% formic acid and acetonitrile on a Zorbax Eclipse C18 column. The mass spectrometric (MS) analysis was carried out in a positive electrospray mode and mitragynine ion (m/z 399.2) was monitored in extracted ion chromatography. A good linearity range was obtained from 10-1000 ng/mL with acceptable accuracy and precision parameters. The microdialysate was collected simultaneously from the striatum and the right jugular vein using microdialysis probes. After a single intravenous administration of 10 mg/kg mitragynine, mitragynine showed a two-compartmental drug elimination pattern with half-life (T1/2) of approximately 13 h. The percent of AUCbrain/AUCplasma of mitragynine was calculated and shown to be 65.8 ± 4.5%. The results indicated that mitragynine could be a suitable molecule to develop into an opioid replacement drug based on its ideal pharmacokinetic properties, namely, small molecular size, lipophilic in nature and with excellent blood–brain barrier (BBB) permeability

Assessment of in vitro antioxidant, antibacterial and immune activation potentials of aqueous and ethanol extracts of phyllanthus niruri

Background: Recently much attention has been paid to biologically active plants because of their low production cost and fewer adverse effects compared with chemical drugs. In the present investigation the bioactivity of Phyllanthus niruri ethanol and aqueous extracts was evaluated in vitro. Results: The ethanol extract of P. niruri showed a high level of flavonoid content (123.9 ± 0.002 mg g -1), while the aqueous extract showed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH; IC 506.85 ± 1.80 μmol L -1) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS; 46.44 ± 0.53 μmol L -1) free radical scavenging activities with high phenol content (376 ± 0.02 mg g -1) and elevated levels of ferric reducing antioxidant power (FRAP; 23 883 ± 0.019 mmol g -1) with excellent antibacterial activity against Staphylococcus aureus (20 mm inhibition zone) and Streptococcus agalactiae (12 mm inhibition zone), respectively, in addition to the best immune activation potential of human peripheral blood mononuclear cells (450.5%). Conclusions: It is clear from our results that both extracts of P. niruri has excellent bioactivity roles via elevated levels of antibacterial, antioxidant and percentage of peripheral blood mononuclear cell proliferation, which could lead to the development of medications for clinical use. © 2012 Society of Chemical Industry

Potential Activity of 3-(2-Chlorophenyl)-1-phenyl-propenonein Accelerating Wound Healing in Rats

Wound healing involves inflammation followed by granular tissue development and scar formation. In this study, synthetic chalcone 3-(2-Chlorophenyl)-1-phenyl-propenone (CPPP) was investigated for a potential role in enhancing wound healing and closure. Twenty-four male rats were divided randomly into 4 groups: carboxymethyl cellulose (CMC) (0.2 mL), Intrasite gel, and CPPP (25 or 50 mg/mL). Gross morphology, wounds treatment with the CPPP, and Intrasite gel accelerate the rate of wound healing compared to CMC group. Ten days after surgery, the animals were sacrificed. Histological assessment revealed that the wounds treated with CPPP showed that wound closure site contained little amount of scar and the granulation tissue contained more collagen and less inflammatory cells than wound treated with CMC. This finding was confirmed with Masson’s trichrome staining. The antioxidant defence enzymes catalase (CAT) and superoxide dismutase (SOD) were significantly increased in the wound homogenates treated with CPPP () compared to CMC treated group. However, in the CPPP treatment group, lipid peroxidation (MDA) was significantly decreased (), suggesting that the CPPP also has an important role in protection against lipid peroxidation-induced skin injury after ten days of treatment with CPPP, which is similar to the values of cytokines TGF-β and TNF-α in tissue homogenate. Finally the administration of CPPP at a dosage of 25 and 50 mg/kg was suitable for the stimulation of wound healing