Onosma bracteatum Wall Aqueous-Ethanolic Extract Suppresses Complete Freund's Adjuvant-Induced Arthritis in Rats via Regulation of TNF-α, IL-6, and C-Reactive Protein.

Onosma bracteatum Wall (O. bracteatum) has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous-ethanolic extract of O. bracteatum leaves (AeOB) in a rat model of complete Freund's adjuvant (CFA)-induced arthritis. Rats were treated with AeOB (250, 500, and 750 mg/kg), indomethacin (10 mg/kg), or a vehicle control from days 8 to 28 post-CFA injection. Arthritic score, paw diameter, and body weight were monitored at regular intervals. X-ray radiographs and histopathological analysis were performed to assess arthritic severity. Inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were quantified by qPCR and icromatography. Phytochemical analysis of AeOB revealed alkaloids, flavonoids, phenols, tannins, Saponins, and glycosides. AeOB also exhibited antioxidant potential with an IC50 of 73.22 µg/mL in a DPPH assay. AeOB and diclofenac exhibited anti-inflammatory and anti-arthritic activities. Rats treated with AeOB at 750 mg/kg and indomethacin showed significantly reduced arthritic symptoms and joint inflammation versus the CFA control. The AeOB treatment downregulated TNF-α and IL-6 and decreased CRP levels compared with arthritic rats. Radiography and histopathology also showed improved prognosis. These findings demonstrate the anti-arthritic potential of AeOB leaves.

A comprehensive review on medicinal plants possessing antioxidant potential.

Many research studies have proposed that about two-thirds of the medicinal plant species of the world possess significant antioxidant potential. Antioxidants are very beneficial as they decrease oxidative stress (OS) in cells and hence play their role in management as well as treatment of numerous diseases like cancers, cardiovascular diseases, as well as many inflammatory illnesses. This review comprises the antioxidant potential of numerous parts of medicinal plants like leaves, stems, roots, seeds, fruits, as well as bark. Synthetic antioxidants named butylated hydroxyanisole (BHA) as well as butylated hydroxytoluene (BHT) are extensively employed in foods because of their role as food preservatives. Several natural antioxidants have better efficacy as compared to synthetic antioxidants. These medicinal plants include Geranium sanguineum L., Rheum ribes L., Diospyros abyssinica, Sargentodoxa cuneata Rehd. Et Wils, Pistacia lentiscus, Ficus microcarpa L. fil., Polyalthia cerasoides (Roxb.) Bedd, Cunn, Teucrium polium L., Crataeva nurvala Buch-Ham., Urtica dioica L., Dracocephalum moldavica L., Momordica Charantia L., Acacia auriculiformis A., Bidens pilosa Linn. The Lamiaceae species, Radiata, Leea indica, Pelargonium endlicherianum, Salvia officinalis L., and Uncaria tomentosa (Willd.) DC. The literature study disclosed more side effects of synthetic antioxidants (including food additives) in comparison with natural antioxidants and for prevention of many diseases.

Phytochemical Profiling, In Vitro Biological Activities, and In-Silico Studies of Ficus vasta Forssk.: An Unexplored Plant.

Ficus vasta Forssk. (Moraceae family) is an important medicinal plant that has not been previously investigated for its phytochemical and biological potential. Phytochemical screening, total bioactive content, and GCMS analysis were used to determine its phytoconstituents profile. Antioxidant, antibacterial, antifungal, anti-viral, cytotoxicity, thrombolytic, and enzyme inhibition activities were examined for biological evaluation. The plant extract exhibited the maximum total phenolic (89.47 ± 3.21 mg GAE/g) and total flavonoid contents (129.2 ± 4.14 mg QE/g), which may be related to the higher antioxidant potential of the extract. The extract showed strong α-amylase (IC50 5 ± 0.21 µg/mL) and α-glucosidase inhibition activity (IC50 5 ± 0.32 µg/mL). Significant results were observed in the case of antibacterial, antifungal, and anti-viral activities. The F. vasta extract inhibited the growth of HepG2 cells in a dose-dependent manner. The GCMS analysis of the extract provided the preliminary identification of 28 phytocompounds. In addition, the compounds identified by GCMS were subjected to in silico molecular docking analysis in order to identify any interactions between the compounds and enzymes (α-amylase and α-glucosidase). After that, the best-docked compounds were subjected to ADMET studies which provide information on pharmacokinetics, drug-likeness, physicochemical properties, and toxicity. The present study highlighted that the ethanol extract of F. vasta has antidiabetic, antimicrobial, anti-viral, and anti-cancer potentials that can be further explored for novel drug development.

A pan-cancer analysis of GINS complex subunit 4 to identify its potential role as a biomarker in multiple human cancers.

This study was initiated to explore the expression variation, clinical significance, and biological importance of the GINS complex subunit 4 (GINS4) in different human cancers as a shared biomarker via pan-cancer analysis through different platforms including UALCAN, Kaplan Meier (KM) plotter, TNMplot, GENT2, GEPIA, DriverDBv3, Human Protein Atlas (HPA), MEXPRESS, cBioportal, STRING, DAVID, MuTarge, Enrichr, TIMER, and CTD. Our findings have verified the up-regulation of GINS4 in 24 major subtypes of human cancers, and its overexpression was found to be substantially associated with poor overall survival (OS), relapse-free survival (RFs), and metastasis in ESCA, KIRC, LIHC, LUAD, and UCEC. This suggested that GINS4 plays a significant role in the development and progression of these five cancers. Furthermore, we noticed that GINS4 is also overexpressed in ESCA, KIRC, LIHC, LUAD, and UCEC patients with different clinicopathological characteristics. Enrichment analysis revealed the involvement of GINS4 associated genes in a variety of diverse GO and KEGG terms. We also explored few significant correlations between GINS4 expression and promoter methylation, genetic alterations, CNVs, other mutant genes, tumor purity, and immune cells infiltration. In conclusion, our results elucidated that GINS4 can serve as a shared diagnostic, prognostic biomarker, and a potential therapeutic target in ESCA, KIRC, LIHC, LUAD, and UCEC patients with different clinicopathological characteristics.

CTHRC1 expression is a novel shared diagnostic and prognostic biomarker of survival in six different human cancer subtypes.

According to the previous reports, the collagen triple helix repeat containing 1 (CTHRC1) causes tumorigenesis by modulating the tumor microenvironment, however, the evidence is limited to a few human cancer subtypes. In the current study, we analyzed and validated the CTHRC1 expression variations in 24 different human cancer tissues paired with normal tissues using publically available databases. We observed that CTHRC1 was overexpressed in all the 24 major subtypes of human cancers and its overexpression was significantly associated with the reduced overall survival (OS) duration of head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), Lung adenocarcinoma (LUAD), stomach adenocarcinoma (STAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that CTHRC1 plays a significant role in the development and progression of these cancers. We further noticed that CTHRC1 was also overexpressed in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of CTHRC1 associated genes in seven diverse pathways. We also explored few interesting correlations between CTHRC1 expression and promoter methylation, genetic alterations, CNVs, CD8+ T immune cells infiltration, and tumor purity. In conclusion, CTHRC1 can serve as a shared diagnostic and prognostic biomarker in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features.

α-Glucosidase Inhibitory, Anti-Oxidant, and Anti-Hyperglycemic Effects of Euphorbia nivulia-Ham. in STZ-Induced Diabetic Rats.

In this study, we aimed to investigate the antidiabetic effects of Euphorbia nivulia (En), native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of En exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of En and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of En with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group (P < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that En possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.

Phytochemical screening and antipyretic effects of hydroalcoholic extracts of selected medicinal plants of Rawalakot, Azad Jammu and Kashmir in albino rats.

Pyrexia occurs due to infection, malignancy and other diseases. Majority of the antipyretic drugs are synthetic in nature which exerts side effects such as gastric ulcer, hepatic necrosis and renal damage. The antipyretic potential of the hydro-alcoholic extracts of Achillea millefolium, Taraxacum officinale, Salix alba and Trigonella foenum were investigated on the yeast-induced pyrexia in albino rats. Paracetamol was used as a positive control. Rectal temperature of albino rats was verified immediately before the administration of the extracts or vehicle or paracetamol and yet again at 1-hour gap for 6 hours using a digital thermometer. The animals having pyrexia were divided into four groups Group1: Paracetamol was given to positive control. Group 2: Distilled water was given to negative control. Group 3: (250mg/kg) extract of the plant was given to rats (treatment group 1). Group 4: (500mg/kg) extracts of the plant was given to albino rats (Treatment group 2). The extracts were also phytochemically screened for alkaloids, tannins, saponins, flavonoids, cardiac glycosides and phenols. The hydro-alcoholic extracts of plants with the dose of 500mg/kg showed significant (p<0.0001) decrease in yeast-induced pyrexia, as compared with that of set drug paracetamol (150mg/kg) where the extract dose 250mg/kg was less effective than that of standard drug (p<0.05). Phytochemical screening showed the presence of alkaloids, tannins, flavonoids, saponins and phenols. This study showed that hydro-alcoholic extracts of all plants under study at a dose of 500mg/kg have significant antipyretic potential in yeast-induced elevated temperature.

HER-2 Positive Breast Cancer - a Mini-Review.

Breast cancer is one of among all cancers with increased incidence, high mortality rate, and high economic and social costs. The the most common type of cancer among females worldwide, breast cancer is actually the uncontrolled proliferation of cells which attain malignancy. Recently it has shown that breast cancer contributes 11% among all types of cancer diagnosed globally on an annual basis and it is one of the leading causes of death among women. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase erbB-2 normally involved in the proliferation and division of breast cells. In some abnormal cases the HER2 gene does not work correctly and makes too many copies of itself. HER2-positive (HER2+) breast cancers constitute an aggressive type of breast cancer and tend to grow faster and are more likely to spread. However, therapies that specifically target HER2, such as Herceptin® (traztuzumab), are very effective. HER2 targeted therapies, has significantly improved the therapeutic outcome for patients with HER2 positive breast cancer.

Phytomedicine-based and Quadruple Therapies in Helicobacter pylori Infection: A Comparative, Randomized Trial.

CONTEXT: Helicobacter pylori (H pylori) is strongly associated with the development of gastritis, duodenal and gastric ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphomas and gastric carcinoma. Emerging antibiotic resistance and patients' poor compliance with modern therapies have resulted in increasing eradication failure. OBJECTIVES: The current trial was conducted to evaluate the efficacy of current quadruple and phytomedicine-based therapies for the eradication of H pylori infection and relief of its associated symptoms in Pakistan. DESIGN: The study was a randomized, controlled, multicenter clinical trial. Setting • The study was conducted in high-risk areas of Pakistan, including at Shifa-Ul-Mulk Memorial Hospital in Karachi, at Bahawalpur Victoria Hospital in Bahawalpur, and at Nawaz Salik Hospital in Rawalpindi. PARTICIPANTS: The study enrolled 210 patients who tested positive for H pylori, 118 males and 92 females. INTERVENTION: Participants were divided into 2 groups according to treatment regimens. One group of participants received quadruple therapy-20 mg of omeprazole, 1g of amoxicillin, 500 mg of metronidazole, and 400 mg of bismuth compound-that was prescribed for 7 d, and another group received an alternate, phytomedicine-based, quadruple formulation-500 mg of Pylorex Plus-that was prescribed for 15 d. OUTCOME MEASURES: The eradication rate for H pylori was the primary outcome measure. Eradication was considered to be achieved on the basis of a negative C-urea breath test (UBT) and a negative stool antigen test for H pylori (HpSAg) at 4 wk after the end of treatment. The secondary outcome measure was the improvement in the clinical features as assessed by dyspepsia scores. RESULTS: In an intention-to-treat (ITT) analysis, the study found that H pylori was eradicated in 56 of the 90 participants in the quadruple therapy group who completed the study (62.2%) and in 48 of the 86 participants in the Pylorex Plus group who completed the study (55.8%). Therefore, Pylorex Plus had an eradication rate comparable with quadruple therapy. However, Pylorex Plus had significantly reduced gastrointestinal (GI) symptoms at the second wk and at 1 mo after treatment, both for participants in whom H pylori was eradicated and for those in whom it was not eradicated. The quadruple therapy group also showed reduced GI symptoms at the second wk and at 1 mo after treatment, but that result occurred only for those participants in whom H pylori was eradicated, and no significant improvement was observed for participants in whom it was not eradicated. CONCLUSIONS: Current quadruple and alternate therapies yielded poor eradication rates (<70%), but the latter produced marked symptomatic improvement, both for participants in whom H pylori was eradicated and for those in whom it was not eradicated, pointing out its potential use with patients with functional dyspepsia (FD) who are both positive and negative for H pylori.

Risk Factors and Epidemiology of Gastric Cancer in Pakistan.

Gastric cancer is the 2nd most common cause of death among all cancers and is the 4th most common cancer in the world. The number of deaths due to gastric cancer is about 800,000 annually. Gastric cancer is more common in men as compared to women and is 3rd most common cancer after colorectal and breast cancers in women. A progressive rise in the incidence rate has been observed in females over the last 5 years. The highest incidence of stomach cancer is in China, South America and Eastern Europe. The incidence of gastric cancer has 20 fold variation worldwide. Global variation is linked by two factors which play important role in developing gastric cancer. One is infection with Helicobacter pylori and the 2nd is diet. South Asia is a region with low risk, despite a high prevalence of H.pylori. Gastric carcinoma is common in southern region of India. Gastric cancer is more readily treated if diagnosed early. This study aims to provide awareness about gastric cancer as well as an updated knowledge about risk factors and epidemiology of gastric cancer in Pakistan.

Update knowledge on cervical cancer incidence and prevalence in Asia.

Cervical cancer is the second most common cause of cancer-related death among women worldwide, with over 500,000 new cases diagnosed annually and 50% mortality rate in Asia. In the United States, approximately 10,370 new cases of cervical cancer are diagnosed annually, and estimated 3,710 deaths occur from the disease, making it the sixth most common cause of malignancy among American women. This study aims to provide awareness about cervical cancer as well as an updated knowledge about the prevalence and incidence of cervical cancer in Asia.

Medicinal plants combating against cancer--a green anticancer approach.

Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities, and morbidities around the world. It is the second leading cause of death all over the world. Although great advancement have been made in the treatment of cancer progression, still significant deficiencies and room for improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies, such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects. However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists are required to find new lead anticancer constituent to fight disease. This review will help researchers in the finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro and in vivo.

Prevalence, risk factors and disease knowledge of breast cancer in Pakistan.

Breast cancer is the most common cancer in females all over the world with approximately one million new cases each year as well as one of second leading causes of death among females. In Pakistan, the most frequently diagnosed cancer among females is also breast cancer, accounting for nearly one in nine female patients. Its incidence in Pakistan is 2.5 times higher than that in neighboring countries like Iran and India. The risk factors associated with breast cancer are age, family history, early menarche, intake of combined estrogen and progestin menopausal hormones, alcohol consumption, physical inactivity, low socioeconomic status and lack of awareness regarding the disease. This mini-review article aims to provide awareness about breast cancer as well as an updated knowledge about the prevalence, risk factors and disease knowledge of breast cancer in Pakistan.