Phytocompounds as potential inhibitors of mycobacterial multidrug efflux pump Rv1258c: an in silico approach.

The number of infections and deaths caused by multidrug resistant (MDR) tuberculosis is increasing globally. One of the efflux pumps, that makes Mycobacterium tuberculosis resistant to a number of antibiotics and results in unfavourable treatment results is Tap or Rv1258c. In our study, we tried to utilize a rational drug design technique using in silico approach to look for an efficient and secure efflux pump inhibitor (EPI) against Rv1258c. The structure of Rv1258c was built using the homology modeling tool MODELLER 9.24. 210 phytocompounds were used for blind and site-specific ligand docking against the modelled structure of Rv1258c using AutoDock Vina software. The best docked plant compounds were further analysed for druglikeness and toxicity. In addition to having excellent docking scores, two plant compounds-ellagic acid and baicalein-also exhibited highly desirable drug-like qualities. These substances outperform more well-known EPIs like piperine and verapamil in terms of effectiveness. This data shows that these two compounds might be further investigated for their potential as Rv1258c inhibitors.

Computational approaches for evaluation of isobavachin as potential inhibitor against t877a and w741l mutations in prostate cancer.

Prostate cancer is the World's second most common cancer, with the fifth-highest male mortality rate. Point mutations such as T877A and W741L are frequently seen in advanced prostate cancer patients, conferring drug-resistance and hence driving cancer growth. Such occurrence of drug resistance in prostate cancer necessitates designing of suitable ligands to ensure better interactions with the receptors which can block the progression of the disease. The present study focus on the modification of plant-derived flavonoids that might act as inhibitors against such point mutations namely, T877A and W741L. In T877A mutation threonine is substituted by alanine at the 877 codon and W741L mutation, tryptophan is substituted by lysine at the 741 codon in prostate cancer. The study revolved on the aspect of the evaluation of Isobavachin and its derivatives as a potential agent to tackle such point mutations by using the in silico approach. A total of 98 molecular dockings were performed to find the ligand-receptor complexes with the lowest binding energy employing Autodock Software to conduct the blind and site-specific docking. Additionally, ligands were screened for Drug-likeness and toxicity using several tools yielding eight possible drug candidates. Based on the results of Molecular Docking, Drug-likeness, and ADMET testing, ten structures, including six complexes and three receptors were subjected to molecular dynamics simulation of 100 ns covering RMSD, RMSF, Rg, and MM/PBSA. Based on the simulation results, Isobavachin, IsoMod4, and IsoMod7 were concluded to be stable and exhibited potential properties for developing a novel drug to combat prostate cancer and its associated drug-resistance.Communicated by Ramaswamy H. Sarma.

In Silico Approach for Phytocompound-Based Drug Designing to Fight Efflux Pump-Mediated Multidrug-Resistant Mycobacterium tuberculosis.

Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is one of the principal causes of death in the world despite the existence of a significant number of antibiotics aimed against it. This is mainly due to the drug resistance mechanisms present in the bacterium, which leads to multidrug-resistant tuberculosis (MDR-TB). Additionally, the development of new antibiotics has become limited over the years. Although there are various drug resistance mechanisms present, efflux pumps are of utmost importance because they extrude out several dissimilar antitubercular drugs out of the cell. There are many efflux pump proteins present in Mycobacterium tuberculosis. Therefore, blocking these efflux pumps by inhibitors can raise the efficacy of the existing antibiotics and may also pave the path for the discovery and synthesis of new drugs. Plant compounds can act as a resource for the development of efflux pump inhibitors (EPIs), which may eventually replace or augment the current therapeutic options. This is mainly because plants have been traditionally used for ages for food or treatment and are considered safe with little or no side effects. Various computational tools are available which are used for the virtual screening of a large number of phytocompounds within a short span of time. This review aims to highlight the mechanism and appearance of drug resistance in Mycobacterium tuberculosis with emphasis on efflux pumps along with the significance of phytochemicals as inhibitors of these pumps and their screening strategy by computational approaches.

Effect of Alternanthera brasiliana (L) Kuntze on healing of dermal burn wound.

Wound healing activity of methanol extract of Alternanthera brasiliana [5% (w/w) ointment] was evaluated in experimental burn wound model in rats. Healing potential was assessed by the rate of wound contraction, estimation of anti-oxidants like catalase, superoxide dismutase, reduced glutathione, protein, vitamin C and hydroxyproline, along with histopathological examination on 8th day post wounding. The statistical data indicated that there was significant increase in wound contraction along with augmented level of antioxidants in granulation tissues in A. brasiliana treated group. Histopathological assessment of the granulation tissue revealed formation of epidermis with keratin layer and deposition of collagen fibers after treatment with the plant extract.

Analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd.

OBJECTIVES: To study the analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd. MATERIALS AND METHODS: Wistar rats and Swiss albino mice were used for studying analgesic and anti-nociceptive activity of Drymaria cordata hydroethanolic extract (DCHE) at doses 50, 100 and 200 mg/kg p.o. Various models viz. acetic acid induced writhing model (female mice), Eddy's hot plate (mice) and tail flick model (rat) for analgesic study and formalin-induced paw licking model (mice) were used for anti-nociceptive study. RESULTS: In acetic acid induced writhing model, effect of DCHE was better than the standard drug- indomethacin 10 mg/kg (p.o.). In the hot plate model, the maximum effect was observed at 60 min at a dose of 200 mg/kg p.o., which was higher than the standard drug morphine sulfate (1.5 mg/kg i.p.), whereas in the tail flick model, effect was comparable with morphine sulfate. In formalin-induced paw licking model, administration of DCHE completely abolished the early phase at 100 and 200 mg/kg p.o. and in the late phase, the effect of DCHE (200 mg/kg p.o.) was higher than indomethacin (10 mg/kg p.o.). CONCLUSION: DCHE was effective in both non-narcotic and narcotic models of nociception, suggesting its possible action via peripheral and central mechanism. It also abolished the early phase in formalin-induced paw licking model, suggesting complete inactivation of C-fiber at higher dose. The activity can be attributed to the phyto-constituents viz tannins, diterpenes, triterpenes and steroids present in the DCHE extract. In conclusion, DCHE can be developed as a potent analgesic and anti-nociceptive agent in future.

Studies on the anti-inflammatory properties of Plantago erosa leaf extract in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Plantago erosa ex Roxb are used traditionally in Northeast India in different illnesses which include wounds, cuts, bruises, insect bites, poison-ivy rashes, minor sores and snakebite, etc. AIM OF THE STUDY: Plantago erosa is one of the commonly used medicinal plants in various inflammatory conditions in this region; however, due to paucity of scientific literature on its anti-inflammatory property, the present study was aimed at evaluating its anti-inflammatory activity in the leaves using in vivo models of inflammation. MATERIALS AND METHODS: Different models like carageenan induced paw edema in rat and mice, formalin induced paw licking in rats and cotton pellet induced granuloma in rats were used for studying the anti-inflammatory activity in methanol extract of Plantago erosa (PEME) leaves. RESULTS: The PEME at the oral doses from 300 to 600 mg/kg showed anti-inflammatory activity in various models. The extract (PEME) reduced carageenan induced paw edema in rat and mice, inhibited the formation of granulomatous tissue in cotton pellet induced granuloma after treatment and also decreased the reaction time in both early and late phases in formalin induced paw licking in rats. CONCLUSION: The study evidently confirmed anti-inflammatory activity of PEME and thus supported the traditional claim. The anti-inflammatory activity could be attributed to the phytoconstituent (flavonoids, alkaloids and steroid) present in the methanol extract of the plant.