Phytochemical and in-vitro Biological Investigation of Indian Traditional Medicinal Plants for their Cytotoxicity and Hepatoprotective Potential.

OBJECTIVE: This study aimed to select 16 medicinal plants based on their folklore remedy for treating various diseases like inflammation, cancer, etc., and scientifically validate their potency. METHODS: Five among them, namely Centella asiatica (CA), Myristica fragrans (MF), Trichosanthes palmata (TP), Woodfordia fruticosa (WF), and Curculigo orchioides (CO), were scientifically confirmed through the extraction and in-vitro cytotoxic and hepatoprotective evaluation. Based on the cytotoxic and hepatoprotective results, the various fractions of CO were chosen for an in-depth phytochemical study to isolate and characterize active compounds by GC-MS. RESULTS: The results showed promising cytotoxic activity (i.e., IC50=<100 µg/ml) against HeLa cell lines and significant hepatoprotective activity in a dose-dependent manner on CCl4 intoxicated isolated hepatocyte cells. CONCLUSION: The present study confirmed the scientific evidence regarding the effectiveness of selected medicinal plants in HeLa and hepatocyte cells. Furthermore, a detailed study on their mechanism of action and clinical application is suggested.

Plant Derived Immunomodulators; A Critical Review.

The concept of immunomodulation was proposed by Edward Jenner, while working on polio vaccine in 1796. Many of the autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, psoriatic arthritis and system lupus erythematosus, viral diseases and, some cancers are characterized with elevated levels of "immunocytokine" gene expression, including, tumor necrosis factor-α, various interleukins, cytotoxic T-cell antigen-4, B-cell activating factor. For the treatment of these diseases, the immunologically-based therapies play the major role. In these lines, the usage of phytomedicines as immunostimulants/ immunosuppressants have been enhanced considerably in last few decades and also used as a prophylactic treatment for various ailments. Phytochemicals such as flavonoids, terpenoids, polysaccharides, lactones, alkaloids, glycosides and saponins present in several plants, have been confirmed to exhibit immunomodulating properties. This review focuses on the traditional plants and their constituents which have been extensively used as immunomodulators. We have also highlighted the mechanism of action of these plant constituents related to autophagy and adjuvanticity of drugs.

Chandamarutha Chenduram, an Indian traditional Siddha preparation attenuated the neuronal degeneration in ischemic mice through ameliorating cytokines and oxy-radicals mediated EAAT-2 dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Chandamarutha Chenduram (CC), an Indian traditional Siddha preparation officially recorded in the Siddha formulary of India and its composition are widely used in the Siddha practice of neurological disorders like stroke/paralysis in India. However, the scientific validation and mechanistic evidence is lacking and yet to be elucidated. AIM OF THE STUDY: To establish the scientific evidences and to explore the possible neuroprotective mechanism of CC in cerebral ischemia. MATERIALS AND METHODS: Chemical standardization of the CC was performed using atomic absorption spectroscopy and gravimetric analysis. Acute toxicity study for CC in mice was performed in accordance with OECD 423 guidelines. CC (5 mg/kg) and CC (10 mg/kg) were investigated in bilateral common carotid occlusion (BCCAo) model in mice. After, behavioral assessments, the brain samples were collected and the hippocampus region was micro-dissected for neurotransmitter, neurobiochemicals and inflammatory cytokines estimation. The excitatory amino acid transporter-2 (EAAT-2) expressions was analyzed by RT-PCR to understand the possible molecular mechanism. In addition, hematoxylin and eosin staining of CA1 hippocampal brain region was performed to support the neuroprotective effect of CC in ischemic condition. RESULTS: Chemical standardization analysis showed that CC has acceptable range of mercury (0.82 ppm) and elemental sulphur (11% w/w). Also, other heavy metal limits were found to be less or not detectable. Toxicity study also evidenced the safety profile of CC. CC has significantly reversed the behavioral dysfunctions (p < 0.001) in global ischemic mice. Treatment with CC has attenuated the excitatory neurotransmitter glutamate, lipid peroxide, nitric oxide, cytokines (IL-1ß, TNF-α) (p < 0.001) and increased the antioxidant enzymes (SOD, CAT, GSH) and EAAT-2 expression level (p < 0.001) in ischemic brain. The hematoxylin and eosin staining in CA1 region of hippocampus also evidence the neuroprotective effect exhibited by CC. CONCLUSIONS: Treatment with CC has exhibited dose dependent effect and CC10 has shown significant protective effect in comparison to CC5 in most of the parameters studied. CC prevented further degeneration of neurons in cerebral ischemic mice through ameliorating inflammatory cytokines and oxy-radicals mediated EAAT-2 dysfunction and subsequent excitotoxicity in neurons.

Enhanced oral bioavailability of an antipsychotic drug through nanostructured lipid carriers.

Olanzapine is an atypical antipsychotic, undergoes extensive first pass metabolism, also has poor aqueous solubility and belongs to BCS (Biopharmaceutical Classification System) Class II drug) exhibit low oral bioavailability. To overcome this and to enhance the bioavailability, intestinal lymphatic transport of drugs can be exploited through Nano structured lipid carriers (NLCs). The NLCs were formulated by solvent diffusion method using solid lipid (glyceryl tripalmitate), liquid lipid (castor oil) and surfactants (Pluronic F-68, Soylecithin). The formulated NLCs were characterized for physico-chemical properties, in-vitro release studies and in-vivo oral bioavailability. F6 has shown average particle size of 158.5 nm with PI of 0.115 indicating narrow particle size distribution and follows uni modal distribution. It was found that the batch with stearyl amine has a zeta potential of 28.39 mV which confers stability to the dispersion. Bioavailability studies indicate that there was more than 5½-fold increase in oral bioavailability in case of NLCs (F6) compared to olanzapine suspension which indicates that NLCs provided sustained release of the drugs, and these systems can be the preferred as drug carriers for lipophilic drugs in long term disease conditions such as schizophrenia for enhanced bioavailability.