TRAIL, an apoptosis inducing cytokine currently in phase II clinical trial, was investigated for its capability to induce apoptosis in six different human tumor cell lines out of which three cell lines showed resistance to TRAIL induced apoptosis. To investigate whether Anacardic acid (A1) an active component of Anacardium occidentale can sensitize the resistant cell lines to TRAIL induced apoptosis, we treated the resistant cells with suboptimal concentration of A1 and showed that it is a potent enhancer of TRAIL induced apoptosis which up-regulates the expression of both DR4 and DR5 receptors, which has been observed in the cellular, protein and mRNA levels. The death receptors upregulation consequent to A1 treatment was corroborated by the activation of p53 as well as phosphorylation of p38 and JNK MAP kinases and concomitant inactivation of NFκβ and ERK signaling cascades. Also, A1 modulated the expression of key apoptotic players like Bax, Bcl-2 and CAD along with the abatement of tumor angiogenesis in vivo in EAT mouse model. Thus, post A1 treatment the TRAIL resistant cells turned into TRAIL sensitive cells. Hence our results demonstrate that A1 can synergize TRAIL induced apoptosis through the upregulation of death receptors and downregulation of anti-apoptotic proteins in cancer context.
Jingini - Lannea coromandelica Merr. (Houtt) is mentioned in Bhava Prakasha Nighantu and Bhavamishra advocates JINGINI for Hridroga. An experimental study was designed with a Model - Isoproterenol (ISO) Induced Cardiac toxicity in order to prove the efficacy of JINGINI for its Cardioprotective activity. Animals were administered with Aqueous and Methanolic extract of JINIGINI in higher and lower dose. The Acute toxicity studies were conducted up to 5000 mg/kg body weight in accordance with OECD 425 guidelines. The higher dose calculated from 1/5th of 5000 mg/kg body weight which summed up to 1000 mg/kg body weight and lower dose calculated from 1/10th of 5000 mg/kg body weight was concluded as 500 mg/kg body weight. The Methanolic extract of JINGINI in Higher and Lower dose (1000 mg/kg body weight and 500 mg /kg body weight respectively) was found to be efficacious in providing the Cardio-protective action in SD Rats.
Rajakshavaka a drug, mentioned in Brimhaniya Maha Kashaya Gana of Charaka is mentioned as Dugdhika by Chakrapani in his commentary and in Bhava Prakasha KC Chunekar commentary, 4 sources are mentioned for the same. Among 4 sources only 2 sources are locally available i.e., Euphorbia hirta Linn and Euphorbia thymifolia Linn. These 2 sources were selected to evaluate Brimhana (Anabolic) action experimentally to understand the better source plant for Dugdhika among locally available sources. The objective of the Study is to experimentally evaluate the drug Dugdhika (Europhobia hirta Linn. Europhobia thymifolia Linn) with respect to its anabolic activity. Anabolic activity was estimated in Wistar rats by administering Hydro-alcoholic extract of Euphorbia hirta Linn (HAEEH) and Euphorbia thymifolia Linn (HAEET) with Normal and High Protein Diet (HPD: Protein – 39.4%, Fat – 10.0%, Fibre – 4.3%, Carbohydrates - 7.0 %). Anabolism was evidenced by physical parameters (Weight, Nose to Anus length, Chest Circumference, Abdominal circumference, BMI), Lean body mass (LBM), Fat body mass (FBM) and Biochemical and Haematological parameters. Both the sources of Dugdhika (Euphorbia hirta Linn and Euphorbia thymifolia Linn) showed significant anabolic action. But, among the two sources Euphorbia thymifolia Linn was more significant compared to Euphorbia hirta Linn with HPD. The obtained results revealed that, among the two locally available sources of Dugdhika (Euphorbia hirta Linn and Euphorbia thymifolia Linn) Euphorbia thymifolia Linn is a better source plant for Brimhana action.
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