Analysis of Peganum harmala, Melia azedarach and Morus alba extracts against six lethal human cancer cells and oxidative stress along with chemical characterization through advance Fourier Transform and Nuclear Magnetic Resonance spectroscopic methods towards green chemotherapeutic agents.

Traditional medicines implicate consumption of plant crude extracts, which may consist of extensive phytochemical diversity. Overall, the most biologically active extract of Peganum harmala (seeds) exhibited significant cytotoxic activity on Artemia salina with LC50 value of 61.547 µg/mL, while P. harmala (roots) [LC50 = 124.229 µg/mL] and M. azedarach (fruits) [LC50 = 147.813 µg/mL] showed moderate cytotoxic potential. P. harmala (seeds) extract also showed the maximum antitumor potential with 52.278 µg/mL LC50. Branches of P. harmala and Morus alba were not active in both bioassays. These outcomes were further reinforced by the levels of phenolics and flavonoids checked against gallic acid and quercetin equivalents, respectively, by standard curves. Current study aims to isolate, structurally characterize and analyze the bioactive compound from plant extracts by using chromatographic and spectrophotometric techniques. Bioactivity guided isolation of extracts led to the isolation of PH-HM-16 from ethyl acetate fraction P. harmala seeds. Chemical structure of PH-HM-16 was elucidated by ESI-MS, 1H NMR, 13C NMR, HSQC and IR spectrum. The results demonstrated significant positive anticancer activities against six human cancer cell lines assessed through MTT cancer cell growth inhibition assay. PH-HM-16 was most effective against prostate cancer cell lines [IC50 = 17.63 µg/mL] followed by breast cancer cell line MCF7 [IC50 value of 41.81 µg/mL]. IC50 value of PH-HM-16 against human myeloid leukemia cell line HL-60 and human colorectal tumor cells HCT-116 was observed as 68.77 µg/mL and 71.54 µg/mL respectively. The IC 50 value of PH-HM-16 compound was not significant against human gastric cancer SGC-7901 (111.89 µg/mL) and human lung adenocarcinoma epithelial cell line A549 (176.04 µg/mL). Isolated bioactive metabolite PH-HM-16 possesses significant antitumor potential so this could be the first step to develop an effective anticancer agent. Hence, this compound represents a promising potential to be chemically standardized or developed into pharmaceuticals for the chemoprevention and/or the treatment of certain types of cancer, especially as adjuvant phytotherapeutics in conventional chemotherapy.

Multi-element uptake and growth responses of Rice (Oryza sativa L.) to TiO2 nanoparticles applied in different textured soils.

The aim of present work was to evaluate the effects of titanium dioxide nanoparticles (TiO2 NPs) on rice's growth (Oryza sativa L.) and nutrient availability under different soil textures. Greenhouse experiment was carried out with three soil textures (sandy loam, silt loam and silty clay loam) and two concentrations of TiO2 NPs (500, 750 mg kg-1). Control (without TiO2 NPs) was also maintained for the comparison. Growth parameters including chlorophyll content, root/shoot length, fresh/dry biomass and nutrients' uptake including calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorous (P), potassium (K) and zinc (Zn) were determined. The results revealed that application of 500 mg kg-1 TiO2 NPs in silty clay loam soil increased the chlorophyll content (3.3-folds), root length (49%), shoot length (31%), root and shoot biomass (41% & 39%, respectively) as compared to other soil textures. The maximum plant growth was observed in silty clay loam > silt loam > sandy loam. Concentration of Cu, Fe, P and Zn in shoot was increased by 8 - , 2.3 - , 0.4 - , 0.05 -folds in silty clay loam upon 500 mg kg-1 TiO2 NPs application as compared to the control. Backward selection method to model the parameters (nutrients in soil) for the response variables (root/shoot length and biomass) showed that Ca, Fe, P are the main nutrients responsible for the increase in plant length and biomass. Overall, the growth of rice was better in silty clay loam at 500 mg kg-1 of TiO2 NPs.

Bioenergetic effects of hydrogen sulfide suppress soluble Flt-1 and soluble endoglin in cystathionine gamma-lyase compromised endothelial cells.

Endothelial dysfunction is a hallmark of preeclampsia, a life-threatening complication of pregnancy characterised by hypertension and elevated soluble Fms-Like Tyrosine Kinase-1 (sFlt-1). Dysregulation of hydrogen sulfide (H2S) by inhibition of cystathionine γ-lyase (CSE) increases sFlt-1 and soluble endoglin (sEng) release. We explored whether compromise in CSE/H2S pathway is linked to dysregulation of the mitochondrial bioenergetics and oxidative status. We investigated whether these effects were linked to CSE-induced sFlt-1 and sEng production in endothelial cells. Here, we demonstrate that CSE/H2S pathway sustain endothelial mitochondrial bioenergetics and loss of CSE increases the production of mitochondrial-specific superoxide. As a compensatory effect, low CSE environment enhances the reliance on glycolysis. The mitochondrial-targeted H2S donor, AP39, suppressed the antiangiogenic response and restored the mitochondrial bioenergetics in endothelial cells. AP39 revealed that upregulation of sFlt-1, but not sEng, is independent of the mitochondrial H2S metabolising enzyme, SQR. These data provide new insights into the molecular mechanisms for antiangiogenic upregulation in a mitochondrial-driven environment. Targeting H2S to the mitochondria may be of therapeutic benefit in the prevention of endothelial dysfunction associated with preeclampsia.

Taxonomic study of one generic and two new species record to the flora of Pakistan using multiple microscopic techniques.

Recent field exploration and collections has led to the findings of several new species in Pakistan. Here we reported two new species Ajuga reptance L and Sphagneticola trilobata (L.) Prusk for the first time in Pakistan flora as these species were neither listed in any other literature nor identified before in Pakistan. These species were found as a result of taxonomic studies performed in the year 2019 in District Rawalpindi and Islamabad, Pakistan. Microscopic techniques were used for the confirmation of foliar epidermal and pollen micromorphological features. Detailed study (morphological, palynological, and foliar epidermal) was provided for the correct identification and delimitation of the species using both light and scanning electron microscopy. Morphological results were compared with the flora of Taiwan and China.