Potential anxiolytic therapeutics from Hybanthus enneaspermus (L.) F. Muell. - mitigate anxiety by plausibly modulating the GABAA-Cl- channel.

Anxiety is a commonly prevailing psychological disorder that requires effective treatment, wherein phytopharmaceuticals and nutraceuticals could offer a desirable therapeutic profile. Hybanthus enneaspermus (L.) F. Muell. is a powerful medicinal herb, reportedly effective against several ailments, including psychological disorders. The current research envisaged evaluating the anxiolytic potential of the ethanolic extract of Hybanthus enneaspermus (EEHE) and its toluene insoluble biofraction (ITHE) employing experimental and computational approaches. Elevated Plus Maze, Light and Dark Transition, Mirror Chamber, Hole board and Open field tests were used as screening models to assess the antianxiety potential of 100, 200 and 400 mg/Kg body weight of EEHE and ITHE in rats subjected to social isolation, using Diazepam as standard. The brains of rats exhibiting significant anxiolytic activity were dissected for histopathological and biochemical studies. Antioxidant enzymes like catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase; and neurotransmitters viz. monoamines (serotonin, noradrenaline, dopamine), Gamma-aminobutyric acid (GABA), and glutamate were quantified in the different regions of rats' brain (cortex, hippocampus, pons, medulla oblongata, cerebellum). Chromatographic techniques were used to isolate phytoconstituents from the fraction exhibiting significant activity that were characterized by spectroscopic methods and subjected to in silico molecular docking. ITHE at 400 mg/Kg body weight significantly mitigated anxiety in all the screening models (p < 0.05), reduced the inflammatory vacuoles and necrosis (p < 0.05) and potentiated the antioxidant enzymes (p < 0.05). It enhanced the monoamines and GABA levels while attenuating glutamate levels (p < 0.01) in the brain. Three significant flavonoids viz. Quercitrin, Rutin and Hesperidin were isolated from ITHE. In silico docking studies of these flavonoids revealed that the compounds exhibited substantial binding to the GABAA receptor. ITHE displayed a promising pharmacological profile in combating anxiety and modulating oxidative stress, attributing its therapeutic virtues to the flavonoids present.

Phytoconstituents from Piliostigma foveolatum (Dalzell) Thoth. leaves induce antiproliferative effect, apoptosis, and cell cycle arrest in Hop-62 cells.

The study evaluated the therapeutic potential of ethanolic leaf extract of Piliostigma foveolatum (Dalzell) Thoth. (EEBF), its toluene, ethylacetate, methanol soluble fractions (viz. TFBF, EFBF, MFBF), and isolated phytoconstituents against lung cancer. Four compounds were isolated from MFBF by column chromatography and preparative HPLC. Structures were elucidated by IR, 13C-NMR, 1H-NMR, mass spectroscopy and identified as Quercetin, Kaempferol, Isorhamnetin, and ß-glucogallin. EEBF and its biofractions exhibited remarkable antiproliferative activity with GI50<85µg/mL, while isolated Quercetin, Kaempferol, Isorhamnetin, and ß-Glucogallin displayed GI50 values of 56.15 ± 1.16 µM, 68.41 ± 3.98 µM, 55.08 ± 0.57 µM and 58.99 ± 12.39 µM respectively. MFBF demonstrated significant apoptotic activity with 42.24 ± 0.57% cells in early and 4.61 ± 0.88% cells in late apoptosis comparable to standard Doxorubicin. Kaempferol exhibited 23.03 ± 0.37% cells in early and 2.11 ± 0.55% cells in late apoptosis, arresting Hop-62 cells in S-phase. In silico molecular docking, revealed that isolated constituents effectively bound to the same binding site of caspase-3 as Doxorubicin, highlighting their apoptotic mode of action.