ABSTRACT
Ajuga bracteosa (Ab) has tremendous medicinal value with long-established disease curing potential. The present study aimed to assess the hepatoprotective potential of Ab extracts in paracetamol-induced hepatotoxicity in mice. Group I (normal control) were treated with saline 1 ml/kg BW orally for 7 days while Group II (toxicant control) received saline 1 ml/kg BW for 6 days and Paracetamol (1000 mg/kg BW) on day7of the treatment. Group III received Standard drug silymarin (100 mg/kg BW) for 6 days and Paracetamol (1000 mg/kg BW) on day 7of treatment. Groups IV andV were administered with methanol extract (ME) 200 mg/kg BW and aqueous extract (AE) 1000 mg/kg BW for 6 days and Paracetamol (1000 mg/kg BW) on day 7th of the study. Both extracts showed hepatoprotective potential against the toxic effects of paracetamol, evidenced by serum analysis of biomarkers involved in liver injury and histopathological findings. Hepatotoxic mice pretreated with Ab plant extract or silymarin exhibited significant decrease in ALP, AST, and ALT enzyme level while GSH levels were markedly increased. According to histological observations, groups treated with PCM (toxicant control) showed significant necrosis and lymphocyte infiltration, while groups treated with silymarin and Ajuga bracteosa plant extract showed preservation of the normal liver structural features. The phytochemical analysis of ME and AE of Ab showed the presence of glycosides, phenolic compounds, tannins, fats, saponins, flavonoids, terpenes, oils, and fats. The antioxidant activity of these two extracts was determined by nitric oxide assay, DPPH assay, and ferric reducing power assay. The methanolic extract exhibited the highest antioxidant potential (78.09 ± 0.0806). The antioxidant potential of aqueous extract was 73.08 ± 0.248. The reducing power for methanolic extract and ascorbic acid (standard) 500 µg/ml was 0.933 and 0.987 respectively. The anti-inflammatory activity of both extracts was demonstrated by in vitro methods, namely albumin denaturation, proteinase inhibition, and membrane stabilization assays. The study suggests that Ab extracts have competence for attenuating inflammation, oxidants, and hepatotoxicity.
ABSTRACT
Cancer continues to increase global morbidity and mortality rates. Despite substantial progress in the development of various chemically synthesized anti-cancer drugs, the poor prognosis of the disease still remains a big challenge. The most common drawback of conventional cancer therapies is the emergence of drug resistance eventually leading to the discontinuation of chemotherapy. Moreover, advanced target-specific therapies including immunotherapy and stem cell therapy are expensive enough and are unaffordable for most patients in poorer nations. Therefore, alternative and cheaper therapeutic strategies are needed to complement the current cancer treatment approaches. Phytochemicals are bioactive compounds produced naturally by plants and have great potential in human health and disease. These compounds possess antiproliferative, anti-oxidant, and immunomodulatory properties. Among the phytochemicals, flavonoids are very effective in treating a wide range of diseases from cardiovascular diseases and immunological disorders to cancer. They scavenge reactive oxygen species (ROS), inhibit cancer metastasis, modulate the immune system and induce apoptotic or autophagic cell death in cancers. This review will discuss the potential of various phytochemicals particularly flavonoids in attempts to target various cancers.
ABSTRACT
Mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cellular growth, development, survival, and metabolism through integration of diverse extracellular and intracellular stimuli. Additionally, mTOR is involved in interplay of signalling pathways that regulate apoptosis and autophagy. In cells, mTOR is assembled into two complexes, mTORC1 and mTORC2. While mTORC1 is regulated by energy consumption, protein intake, mechanical stimuli, and growth factors, mTORC2 is regulated by insulin-like growth factor-1 receptor (IGF-1R), and epidermal growth factor receptor (EGFR). mTOR signalling pathways are considered the hallmark in cancer due to their dysregulation in approximately 70% of cancers. Through downstream regulators, ribosomal protein S6 kinase ß-1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), mTORC1 influences various anabolic and catabolic processes in the cell. In recent years, several mTOR inhibitors have been developed with the aim of treating different cancers. In this review, we will explore the current developments in the mTOR signalling pathway and its importance for being targeted by various inhibitors in anti-cancer therapeutics.
ABSTRACT
Background and objectives: Abnormal uterine bleeding is a significant clinical and gynaecological concern that necessitates its safe and effective treatment. The present study aims to compare the cost-effectiveness, safety, efficacy, and health-related quality of life of ormeloxifene with medroxyprogesterone acetate in women with non-structural abnormal uterine bleeding. Materials and Methods: A prospective, randomized, single-blinded clinical trial of 367 patients was carried out at a tertiary care hospital for a period of one year from 5 January 2019 to 4 January 2020. Patients were randomized into two groups for administering ormeloxifene and medroxyprogesterone acetate for a 3-month treatment duration and were evaluated by laboratorial investigations like anaemic status, bleeding duration, endometrial thickness, pictorial blood loss assessment chart (PBLAC) score, and patient's medical and medication history. Health-related quality of life was assessed using short form survey-36 (SF-36) questionnaire scale. Cost-effectiveness was determined on the basis of the three-month treatment regimen. Results: The mean duration of bleeding reduced from 16.88 ± 6.46 to 7.76 ± 1.55 in the ormeloxifene group and from 15.91 ± 5.04 to 8.7 ± 1.91 (p < 0.001) in the medroxyprogesterone acetate. Similarly, mean haemoglobin increased from 8.56 ± 0.77 to 10.1 ± 0.087 g/dL and from 8.60 ±0.97 to 9.551 ± 0.90 g/dL (p < 0.001), and endometrial thickness showed a reduction from 8.52 ± 1.61 mm to 6.92 ± 1.68 mm and from 8.40 ± 2.09 mm to 7.85 ± 2.0 mm (p < 0.001) in the ormeloxifene and medroxyprogesterone acetate groups, respectively. PBLAC score reduced from 289.92 ± 42.39 to 128.11 ± 33.10 and from 287.38 ± 40.94 to 123.5 ± 29.57 (p < 0.001) in these groups, respectively. Health-related quality of life improved in the ormeloxifene group more than the medroxyprogesterone group, which was evidenced by SF-36 scale parameters (physical function, energy/fatigue and pain) that changed from 24.39, 12.99, 6.25 to 28.95, 18, 9 and from 25.41, 13.6, 7.1 to 27.02, 16, 8.3 in the ormeloxifene and medroxyprogesterone acetate groups, respectively. Conclusions: The study concludes that both medroxyprogesterone acetate and ormeloxifene are safe and efficacious in controlling abnormal uterine bleeding, but ormeloxifene was the better of the two in terms of cost effectiveness, reduction in pictorial blood loss assessment score, endometrial thickness, bleeding duration (days), increase in haemoglobin concentration (g/dL) and improvement in the quality of life.
