Antibacterial activity of selected medicinal plants of northwest Pakistan traditionally used against mastitis in livestock

The present study aimed to investigate the efficacy of traditionally used anti-mastitis plants (Allium sativum, Bunium persicum, Oryza sativa and Triticum aestivum) in northwest Pakistan against bacterial pathogens. Selected plants were phytochemically screened for Alkaloids, Flavonoids, and Saponins and checked for in vitro antibacterial activity at concentration of 50 mg/ml against S. aureus, E. coli and K. pneumoniae by agar well diffusion method. Minimum inhibitory concentration and minimum bactericidal concentration was determined against multidrug resistant bacteria using tube dilution method. All extracts were found to significantly inhibit (p < 0.01, p < 0.05) the activity against bacterial strains examined. Among phytochemicals, alkaloids of all tested antimastitis plants produced significantly higher inhibition zones against bacteria. The minimum inhibitory concentration and minimum bactericidal concentration of phytochemicals and crude methanolic extracts against tested bacterial strains ranged between 12.5–50 mg/ml and 25–50 mg/ml, respectively. Medicinal plants traditionally used against mastitis are therapeutically active against bacterial pathogens. A. sativum and B. persicum were found to be potential candidate species for the development of novel veterinary drugs with low cost and fewer side effects.     

Ethnomedicinal assessment of Irula tribes of Walayar valley of Southern Western Ghats,India

The present study was aimed to explore the traditional knowledge of Irula tribal people who are practicing herbal medicine in Walayar valley, the Southern Western Ghats, India. A total number of 146 species of plants distributed in 122 genera belonging to 58 families were identified as commonly used ethnomedicinal plants by them. Interestingly, 26 new claims were also made in the present study. Through the data obtained from Irula tribal healers, the herbs were mostly used for medicine (40.4%) followed by trees (26.7%) and climbers (18.5%). In addition leaves were highly used for medicinal purposes, collected from 55 species (38%) followed by multiple parts from 18 species (12%). Acorus calamus is the species of higher use value (1.80) assessed to be prescribed most commonly for the treatment of cough. High informant consensus factor (1.0) obtained for insecticidal uses and cooling agent indicates that the usage of Canarium strictum and Melia dubia, and Mimosa pudica and Sesamum indicum respectively for that purposes had obtained high degree of agreement among the healers in using these species for the respective purposes. The most commonly used method of preparation was decoction (63%) followed by raw form (23%), paste (12%) and powder (2%). Therefore, it is suggested to take-up pharmacological and phytochemical studies to evaluate the species to confirm the traditional knowledge of Irulas on medicinal plants.     

Comparative Gametogenesis and Biochemical Differentiation of Goatfish (<Emphasis Type="Italic">Parupeneus heptacanthus</Emphasis> and <Emphasis Type="Italic">Parupeneus cyclostomus</Emphasis>) from Red Sea

Red Sea’s goatfish (Mullidae), locally referred as ‘Sultan Ibrahim’, are a popular recreational fish that also supports neighboring commercial markets. The present study compares spermatogenesis, oogenesis and gonad structure, in two species of goatfish from Jeddah coast. The reproductive parameters including changes in gonado-somatic index (GSI),and spawning seasons were analyzed for Parupeneus heptacanthus (cinnabar goatfish) and Parupeneus cyclostomus (goldsaddle goatfish). P. heptacanthus spawn from February to June and P. cyclostomus spawning season begins from August to September. Remarkable difference in the egg size has been observed P. heptacanthus had the egg diameter (325.9 μm), while the smallest one is P. cyclostomus (209.6 μm) when compared to other species of Mullidae. P. heptacanthus was observed with largest flagellum length (8.7 ± 0.2 μm). The ultrastructure revealed some common features in both species like oval ova; further the ovarian follicular epithelium consists of two layers, an inner granulosa layer with zona radiata under them and an outer theca layer. Centrioles of both species consist of the typically arranged nine triplets (9 + 0) of microtubules. The external lay of zona radiata is thinner than internal one. Disparity in protein patterns of muscle and gonads were observed in the present study. There was also variation in the number of specific bands for each species in both protein soluble muscle and gonads. The histology results reported gonads to be typically gonochoristic and exhibited asynchronous development of oocytes in the ovary. The outcome of this study has yielded essential information of some of the imperative reproductive biology of P. heptacanthus and P. cyclostomus.     

Induction of apoptosis by pyrazolo[3,4-d]pyridazine derivative in lung cancer cells via disruption of Bcl-2/Bax expression balance

In the rapidly expanding era of cancer target therapy, regulators of apoptosis are emerging as attractive therapeutic targets. X-linked inhibitor of apoptosis (XIAP) is of specific interest owing to its characteristic overexpression in a wide variety of neoplasms, with a resultant survival advantage for tumor cells and treatment resistance. In this study, we examined three pyrazolo [3,4-d] pyridazine derivatives (PPDs) through molecular modeling and studied their modes of interaction with XIAP-BIR3 domain. PPD-1, which possessed the highest binding affinity with XIAP, was tested on A549 (lung cancer cell line); HCT-116 (colorectal carcinoma cell line); HEPG2 (liver carcinoma cell line), HFB4 (normal human skin melanocyte cell line) and WI-38 (human embryonic lung fibroblasts). In comparison to cisplatin as a positive control, PPD-1 yielded remarkable cytotoxicity on all cancer cell lines, with the highest anti-tumor activity on A549 and a favorable therapeutic ratio. Flow cytometry studies concluded that PPD-1 treatment induces Sub G1 and G2/M cell cycle arrest and apoptosis. The percentage of apoptotic cells in PPD-1 treated A549 cells was considerably higher than that in untreated cells (10.06% vs 0.57%, respectively). To further investigate the mechanism of induction of apoptosis by PPD-1, Real time-PCR was used to quantify the expression levels of key apoptotic regulators. Significant overexpression of the effector capsase-3, pro-apoptotic bax and tumor suppressor gene p53 were noted as compared to untreated cells (7.19 folds, 7.28 folds, and 5.08 folds, respectively). Moreover, PPD-1 inhibited the expression of the anti-apoptotic bcl-2 gene to 0.22 folds. These findings demonstrate that PPD-1 treatment disrupts the Bcl-2/BAX balance in lung cancer cell lines, leading to apoptosis induction possibly through intrinsic mitochondria-dependent pathway. These novel insights elucidate the mechanism of PPD-1 cytotoxicity in lung cancer cell lines and offer a promising therapeutic approach that needs further study.     

Monitoring of trace metals in tissues of Wallago attu (lanchi) from the Indus River as an indicator of environmental pollution

We aimed to assess the bioaccumulation of selected four trace metals (Cd, Ni, Zn and Co) in four tissues (muscles, skin, gills and liver) of a freshwater fish Wallago attu (lanchi) from three different sites (upstream, middle stream and downstream) of the Indus River in Mianwali district of Pakistan. Heavy metal contents in water samples and from different selected tissues of fish were examined by using flame atomic absorption spectrometry. The data were statistically compared to study the effects of the site and fish organs and their interaction on the bioaccumulation pattern of these metals at P < 0.05. In W. attu the level of cadmium ranged from 0.004 to 0.24; nickel 0.003–0.708; cobalt 0.002–0.768 and zinc 47.4–1147.5 μg/g wet weight. The magnitude of metal bioaccumulation in different organs of fish species had the following order gills > liver > skin > muscle. The order of bioaccumulation of these metals was Ni < Zn < Co < Cd. Heavy metal concentrations were increased during the dry season as compared to the wet season. The results of this study indicate that freshwater fish produced and marketed in Mianwali have concentrations below the standards of FEPA/WHO for these toxic metals.     

A comparative gametogenesis and biochemical differentiation of goatfish (Family: Mullidae) from the Red Sea

Comparative study between few species of goatfishes (Mullidae), locally called Sultan Ibrahim, has been investigated from Jeddah coast. The present study compares gonad structure, oogenesis and spermatogenesis in three species of goatfish. The various stages are similar in the different species, but differ in time of spawning. The reproductive biology of three goatfishes, Mulloidichthys flavolineatus (1 black blotch), Mulloidichthys flavolineatus (3 black blotches), Mulloidichthys vanicolensis, were examined. A macroscopic and histological examination of the gonads demonstrated that all the three species are typically gonochoristic. Species-specific reproductive parameters including male stages, changes in gonado-somatic index (GSI), classification of oocyte stages were analyzed for each of the three targeted species. All three species have asynchronous ovary. The spawning season for the three studied species differ from one species to another i.e., the spawning season for M. vanicolensis females and males from April to July; M. flavolineatus, (1 black blotches) for both sexes from May until December; for M. flavolineatus (3 black blotches) showed a peak in May to early October for both sexes. Ultrastructurally the mature spermatozoon’s head shape appears like a computermouse, the tiny mid-piece consist two mitochondria and a flagellum. The chromatin, within the nucleus is electron-dense and homogenous in M. flavolineatus (with one black blotch), while the chromatin is granular in (M. vanicolensis and M. flavolineatus (3 black blotches)). The posterior region of the nucleus is deeply penetrated by the nuclear fossa which contains, the basal part of flagellum and centriolar complex. The ultrastructure of the eggs of the three Mullidae species is circular in shape and contains a simple, circular micropyle. The ovarian follicular epithelium of the three Mullidae species consists of two layers, an outer theca layer and an inner granulosa layer with zona radiata under them. Zona radiata consists of 2 layer-interna and externa. Zona radiata interna is thicker than zona radiata externa. Differences in protein patterns of muscles and gonads were observed in the present study.     

The binding proximity of methyl β-lilacinobioside isolated from Caralluma retrospiciens with topoisomerase II attributes apoptosis in breast cancer cell line

The alterations in somatic genomes that controls the mechanism of cell division as a main cause of cancer, and then the drug that specifically toxic to the cancer cells further complicates the process of the development of the widely effective potential anticancer drug. The side effects of the drug as well as the radiotherapy used for the treatment of cancer is severe; therefore, the search of the natural products from the sources of wild plants having anticancer potential is become immense importance today. The ethno-medicinal survey undertaken in Al-Fayfa and Wadi-E-Damad region of southern Saudi Arabia revealed that the Caralluma retrospiciens (Ehrenb.) N.E.Br. (family Apocynaceae) is being used for the treatment of cancer by the native inhabitants. The biological evaluation of anticancer potential of bioassay-guided fractionations of methanolic extract of whole plant of C. retrospiciens against human breast adenocarcinoma cell line (MCF-7) followed by characterization using spectroscopic methods confirmed the presence of methyl β-lilacinobioside, a novel active constituent reported for the first time from C. retrospiciens, is capable of inhibition of cell proliferation and induction of apoptosis in MCF-7 cells by regulating ROS mediated autophagy, and thus validated the folkloric claim. Based on a small-scale computational target screening, Topoisomerase II was identified as the potential binding target of methyl β-lilacinobioside.     

Nephroprotective effect of pigmented violacein isolated from Chromobacterium violaceum in wistar rats

The present study aimed to analyze the nephroprotective property of violacein obtained from the bacterium, Chromobacterium violaceum. The nephrotoxicity in the animal model was induced by gentamicin, potassium dichromate, mercuric chloride, and cadmium chloride-induced nephrotoxicity in the Wistar rats was analyzed by measuring the serum creatinine, uric acid, and urea level. The present investigation revealed the nephroprotective property on convoluted proximal tubule (S1 and S2 segments) and the straight proximal tubule (S3 segment). Also, violacein significantly improved the renal function by the renal protective property on S2 segment of proximal tubule from the nephrotoxicity stimulated by mercuric chloride, potassium dichromate, cadmium chloride and gentamicin in animal models. Animal model studies revealed that violacein at 20 and 40 mg/kg p.o improved the renal function and significantly reduced the increased amount of uric acid, creatinine, and blood urea compared to the control.