Emerging roles of NAC transcription factor in medicinal plants: progress and prospects.

Transcriptional factors act as mediators in regulating stress response in plants from signal perception to processing the directed gene expression. WRKY, MYB, AP2/ERF, etc. are some of the major families of transcription factors known to mediate stress mechanisms in plants by regulating the production of secondary metabolites. NAC domain-containing proteins are among these large transcription factors families in plants. These proteins play impulsive roles in plant growth, development, and various abiotic as well as biotic stresses. They are involved in regulating the different signaling pathways of plant hormones that direct a plant's immunity against pathogens, thereby affecting their immune responses. However, their role in stress regulation or defence mechanism in plants through the secondary metabolite biosynthesis pathway is studied for very few cases. Emerging concern over the requirement of medicinal plants for the production of biocompatible drugs and antibiotics, the study of these vast, affecting proteins should be focused to improve their qualitative and quantitative production further. In medicinal plants, phytochemicals and secondary metabolites are the major biochemicals that impose antimicrobial and other medicinal properties in these plants. This review compiles the NAC transcription factors reported in selected medicinal plants and their possible roles in different mechanisms. Further, the comprehensive understanding of the molecular mechanism, genetic engineering, and regulation responses of NAC TFs in medicinal plants, can lead to improvement in stress response, immunity, and production of usable secondary metabolites.

Rosmarinic acid attenuates inflammation in experimentally induced arthritis in Wistar rats, using Freund's complete adjuvant.

AIM: The purpose of our investigation is to evaluate the anti-arthritic potential of isolated rosmarinic acid from the rind of Punica granatum. METHOD: Rosmarinic acid was isolated by bioactivity-guided isolation from butanolic fraction of Punica granatum and acute toxicity of rosmarinic acid was carried out. The experiment was conducted at doses of 25 and 50 mg/kg, in Freund's complete adjuvant (FCA)-induced arthritic rats. Various parameters, that is arthritic score, paw volume, thickness of paw, hematological, antioxidant and inflammatory parameters such as glutathione (GSH), superoxide dismutase (SOD), malonaldehyde (MDA) and tumor necrosis factor-α (TNF-α) were also estimated. RESULTS: Rosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate. It also significantly increased body weight, hemoglobin and red blood cells. The significantly decreased levels of TNF-α were observed in treated groups as compared to arthritic control rats (P < 0.001). At the same time antioxidant parameters (like GSH and SOD) were increased significantly while levels of MDA were significantly decreased (P < 0.001). CONCLUSION: The outcome of the present research concludes that rosmarinic acid showed significant anti-arthritic potential in FCA-induced arthritis in Wistar rats. This study represented the therapeutic role of rosmarinic acid from Punica granatum for the management of arthritis/rheumatoid arthritis/osteoarthritis and related inflammatory complications with negligible side effects which was still far from complete mitigation with available conventional medicines.

Evaluation of Antiarthritic Activity of Butanol Fraction of Punica granatum Linn. Rind Extract Against Freund's Complete Adjuvant-Induced Arthritis in Rats.

Available conventional drugs produce several side effects; thus, a potent herbal drug is urgently required for the management of rheumatoid arthritis. The present investigation was performed to evaluate the antiarthritic activity of butanol fraction of Punica granatum Linn. rind methanolic extract (PGBF) against Freund's complete adjuvant (FCA)-induced arthritis in rats. An acute toxicity study of butanol fraction was conducted, accompanied by a study of its antiarthritic activity. Chromatography (thin layer chromatography and high-performance thin layer chromatography) analyses were also conducted. Phytochemical screening of the fraction was performed to confirm the presence of phytoconstituents. For antiarthritic activity, the active butanol fraction was administered at doses of 50 and 75 mg/kg body weight. The antiarthritic activity was evaluated by using biophysical paramaters (arthritic score, body weight, paw volume and joint diameter) and hematological parameters [red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (Hb) concentration and erythrocyte sedimentation rate (ESR)]. Dexamethasone (5 mg/kg) was selected as the standard. Phytochemical screening of butanol fraction showed the presence of steroids, tannins, flavonoids, irioid glycosides, and phenolic compounds. Acute toxicity studies suggested that butanolic fraction was safe up to a dose of 500 mg/kg. The data regarding biophysical and hematological parameters clearly indicated that the butanol fraction at a 75 mg/kg dose showed a more significant effect (**P<0.01 and ***P<0.001) than the 50 mg/kg dose. The antiarthritic potential of a butanol fraction of Punica granatum Linn. rind extract may be due to the presence of active phytoconstituents such as flavonoids, irioid glycosides, and phenolic compounds. Future studies will provide a new approach in relation to the antiarthritic activity of Punica granatum Linn., and the isolation of its active compound may eventually lead to the development of a new category of the antiarthritic agent.

Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response.

Paclitaxel (PTX) is used as first line treatment for metastatic breast cancer but the relief comes at a heavy cost in terms of accompanying adverse effects. The pharmaceutical credentials of PTX are further dampened by the intrinsically low aqueous solubility. In order to sideline such insidious tendencies, PTX was incorporated in a vitamin E nanoemulsion using high pressure homogenization. The encapsulation efficiency of PTX in nanoemulsion was 97.81±2.7% and a sustained drug release profile was obtained. PTX loaded nanoemulsion exhibited higher cytotoxicity in breast cancer cell line (MCF-7) when compared to free PTX and marketed formulation (Taxol). Cell cycle arrest study depicted that MCF-7 cells treated with PTX loaded nanoemulsion showed high arrest in G2-M phase. Moreover blank nanoemulsion induced additional apoptosis in breast cancer cells through G1-S arrest by disrupting mitochondrial membrane potential. Cytokine estimation study in macrophages showed that both PTX loaded nanoemulsion and blank nanoemulsion enhanced secretion of IL-12 and downregulated secretion of IL-4 and IL-10. Results suggest that inclusion of vitamin E in nanoemulsion opened multiple complementary molecular effects which not only magnified the principle antiproliferative activity of PTX but also independently showcased potential in restoring the proactive nature of the breast cancer slackened chronic immune response. In-vivo anticancer activity showed significantly improved efficacy of PTX loaded nanoemlsion compare to Taxol and free PTX. The list of plausible advantages of PTX nanoemulsification was further substantiated by acceptable haemolytic potential, reduced in-vivo toxicity and conveniently modified pharmacokinetic profile in which the AUC and MRT were extended considerably. Overall, there were strong evidences that developed formulation can serve as a viable alternative to currently available PTX options.

Synthesis of novel anticancer iridoid derivatives and their cell cycle arrest and caspase dependent apoptosis.

Nyctanthes arbortristis Linn (Oleaceae) is widely distributed in sub-Himalayan regions and southwards to Godavari, India commonly known as Harsingar and Night Jasmine. In continuation of our drug discovery programme on Indian medicinal plants, we isolated arbortristoside-A (1) and 7-O-trans-cinnamoyl 6ß-hydroxyloganin (2) from the seeds of N. Arbortristis, which exhibited moderate in vitro anticancer activity. Chemical transformation of 2 led to significant improvement in the activity in derivative 8 and 15 against HepG2 (human hepatocellular carcinoma), MCF-7 (breast adenocarcinoma) cell lines. The compounds 8 and 15 were also capable of cell cycle arrest and caspase dependent apoptosis in HepG2 cell lines. These iridoid derivatives hold promise for developing safer alternatives to the marketed drugs.

Preparation of novel antiproliferative emodin derivatives and studies on their cell cycle arrest, caspase dependent apoptosis and DNA binding interaction.

Emodin (1) is the major bioactive compound of several herb species, which belongs to anthraquinone class of compound. As a part of our drug discovery program, large quantities of emodin (1) was isolated from the roots of Rheum emodi and a library of novel emodin derivatives 2-15 were prepared to evaluate their antiproliferative activities against HepG2, MDA-MB-231 and NIH/3T3 cells lines. The derivatives 3 and 12 strongly inhibited the proliferation of HepG2 and MDA-MB-231 cancer cell line with an IC50 of 5.6, 13.03 and 10.44, 5.027, respectively, which is comparable to marketed drug epirubicin (III). The compounds 3 and 12 were also capable of inducing cell cycle arrest and caspase dependent apoptosis in HepG2 cell lines and exhibit DNA intercalating activity. These emodin derivatives hold promise for developing safer alternatives to the marketed epirubicin.

Effect of Convolvulus pluricaulis Choisy and Asparagus racemosus Willd on learning and memory in young and old mice: a comparative evaluation.

A dose dependent enhancement of memory was observed with A. racemosus and C. pluricaulis treatment as compared to control group when tested on second day. A. racemosus and C. pluricaulis at the dose of 200 mg/kg, po showed significantly higher percent retentions, than piracetam. Multiple treatment with A. racemosus and C. pluricaulis for three days also demonstrated significant dose dependent increase in percent retentions as compared to control group. The effect was more prominent with C. pluricaulis as compared with piracetam and A. racemosus. A significantly lower percent retention in aged mice was observed as compared to young mice. Aged mice (18-20 months) showed higher transfer latency (TL) values on first and second day (after 24 h) as compared to young mice, indicating impairment in learning and memory. Pretreatment with A. racemosus and C. pluricaulis for 7 days enhanced memory in aged mice, as significant increase in percent retention was observed. Significantly higher retention was observed with C. pluricaulis (200 mg/kg; po) as compared with piracetam (10 mg/kg/; po). Post-trial administration of C. pluricaulis and A. racemosus extract demonstrated significant decrease in latency time during retention trials. Hippocampal regions associated with the learning and memory functions showed dose dependent increase in AChE activity in CA 1 with A. reacemosus and CA3 area with C. pluracaulis treatment. The underlying mechanism of these actions of A. racemosus and C. pluricaulis may be attributed to their antioxidant, neuroprotective and cholinergic properties.