The Therapeutic Potential of Aged Garlic Extract in the Protection against Doxorubicin-Induced Cardiotoxicity

Doxorubicin (DOX) is a one of the most potent anticancer drug which is widely used in the treatment of childhood and adult cancer. Cardiac toxicity is a dangerous so far unsolved complication of DOX. Doxorubicin-induced cardiotoxicity is attributed to oxidative stress and p53-dependent apoptosis. The establishment of an effective safe compound would be of great benefit in the management of DOX-induced cardiotoxicity. Aged garlic extract (AGE) is a natural, promising compound to lessen DOX-induced cardiotoxicity due to it antioxidant, antiapoptotic, and multiple health promoting effects. This study investigated the protective effect of AGE against DOX-induced cardiotoxicity in Wistar rats and in rat cardiac myocytes. It also investigated the effect of AGE pretreatment on oxidative stress, p53, active caspase-3 and gene expression in DOX-treated rat cardiac myocytes. The results of this study have revealed that AGE protects against DOX-induced cardiotoxicity in vivo and in vitro. Four groups of rats were assessed for serum cardiac enzymes, plasma and heart malonialdehyde (MDA), serum total antioxidant status (TAS), and light and electron microscopic examination of the heart tissue. Serum cardiac enzymes were found to be elevated in DOX-treated rats. The findings of this study have revealed that there is an oxidative stress in DOX-treated rats, as manifested by increased plasma and heart MDA concentrations and reduced serum TAS. Pre-treatment with AGE reduced MDA concentrations and normalised TAS, which are indicators of oxidative stress in DOX-treated rats and attenuated histopathological alterations in DOX-treated rats. Aged garlic extract pre-treatment did not interfere with the cytotoxic activity of DOX, but it augmented DOX uptake into tumour cells in mice bearing EAC and increased the long term survivors of tumour-bearing mice. Pretreatment of rat cardiac myocytes with AGE lowered DOX-induced elevation of 8- isoprostane, p53 and caspase-3 activity. The results of this study demonstrated that pretreatment with AGE insignificantly reduced increased expression of some antioxidant XIV genes in DOX-treated rat cardiac myocytes. Further studies are needed to identify the detailed molecular mechanisms underlying the protective effects of AGE

Aged garlic extract potentiates doxorubicin cytotoxicity in human breast cancer cells

Purpose: To investigate the potential chemo-sensitizing effect of aged garlic extract (AGE) on doxorubicin (DOX) in breast cancer cells (MCF-7), and the possible underlying mechanisms.Methods: Human breast cancer cell line (MCF-7) was treated with AGE and DOX. The cytotoxic effects of AGE and DOX were investigated via cell cycle analysis and apoptosis induction, using flow cytometry. Mechanistic studies involved the determination of cellular uptake of DOX and  p-glycoprotein (P-gp) activity.Results: Combined treatment of MCF7 cells with AGE and DOX produced no significant effect at AGE dose of 10 mg/mL. However, co-treatment with AGE at doses of 50 and 93 mg/mL enhanced the cytotoxicity of DOX on MCF-7 cells, with IC50 values of 0.962 and 0.999 μM, respectively, whencompared with 1.85 μM DOX alone. Moreover, Annexin V-FITC and PI techniques showed that AGE significantly increased percentage of cells in late apoptosis. Besides, AGE-DOX treatment significantly increased cellular uptake of DOX and inhibited P-gp activity, when compared with DOX alone (p < 0.05).Conclusion: AGE enhances the cytotoxic effect of DOX on MCF-7 cells, most likely due to cell cycle distribution, stimulation of apoptosis, increased uptake of DOX by MCF7, and inhibition of P-gp activity. Keywords: Aged garlic extract, Doxorubicin, Breast cancer, MCF-7 cell line, P-glycoprotein, Apoptosis, Cell cycl

Lycorine Ameliorates Thioacetamide-Induced Hepatic Fibrosis in Rats: Emphasis on Antioxidant, Anti-Inflammatory, and STAT3 Inhibition Effects

Liver fibrosis is a foremost medical concern worldwide. In Saudi Arabia, numerous risk factors contribute to its high rates. Lycorine—a natural alkaloid—has antioxidant, anti-inflammatory, and antitumor activates. It has been reported to inhibit STAT3 in cancer. Therefore, this study aimed at investigating the possible antifibrotic effect of lycorine against thioacetamide (TAA)-induced liver fibrosis in rats and at elucidating the possible mechanisms. Liver fibrosis was induced by TAA (200 mg/kg i.p.), three per week for four weeks. Treatment with lycorine (0.5 and 1 mg/kg/d) amended TAA-induced rise of serum transaminases that was confirmed histopathologically. Moreover, it ameliorated liver fibrosis in a dose-dependent manner, as indicated by hindering the TAA-induced increase of hepatic hydroxyproline content, α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-β1) expressions. TAA-induced oxidative stress was amended by lycorine treatment via restoring reduced glutathione and diminishing lipid peroxidation. Moreover, lycorine ameliorated hepatic inflammation by preventing the rise of inflammatory cytokines. Notably, lycorine inhibited STAT3 activity, as evidenced by the decreased phospho-STAT3 expression, accompanied by the elevation of the hepatic Bax/Bcl-2 ratio. In conclusion, lycorine hinders TAA-induced liver fibrosis in rats, due to—at least partly—its antioxidative and anti-inflammatory properties, along with its ability to inhibit STAT3 signaling

Catharanthus roseus Combined with Ursolic Acid Attenuates Streptozotocin-Induced Diabetes through Insulin Secretion and Glycogen Storage

Catharanthus roseus (C. roseus) and ursolic acid (UA) are ayurvedic medicines with multiple pharmacological activities including antidiabetic activity, but till date, no study is available on their combination. This study documented the antidiabetic efficacy of the combination of C. roseus and UA in rats. Rats were divided into six groups. All groups were given a single dose of Streptozotocin (STZ) at a dose of 50 mg/kg by intraperitoneal route for induction of diabetes, except the normal control group. Group 1 was treated as a normal control (NC) group and fed with saline water, Group 2 as a Diabetes Control group, Group 3 as a STZ+C. roseus ethanolic extract (CREE) group at 50 mg/kg p.o., Group 4 as a STZ+UA group orally at 50 mg/kg, Group 5 as a STZ+CREE (25 mg/kg p.o.)+UA (25 mg/kg p.o.) group, and Group 6 as a STZ+Glimepiride (0.1 mg/kg) group. Diabetes was confirmed after 72 hours by estimation of blood glucose level, and then treatment was given for the next 28 days. During the course of treatment, plasma insulin and blood glucose were measured regularly at the interval of 7 days. At the end of the protocol, blood was collected and animals were sacrificed. The glucose level, insulin level, liver glycogen storage level, and antioxidant enzymes (LPO, CAT, SOD, GPx, GST) were measured. The blood glucose level in Group 5 significantly (P<0.001) reduced to 98.35±2.45 mg/dl in comparison with that in Group 2 (321.75±5.46 mg/dl). The level of plasma insulin in Group 5 increased (13.65±0.10 μU/ml) significantly (P<0.01) as compared with that in Group 2 (05.93±0.31 μU/ml). In Group 5, the level of glycogen in liver was significantly (P<0.01) increased as compared with that in Group 2 rats. The level of antioxidant enzymes in Group 5 restored toward normal values significantly (P<0.01; P<0.001) as compared with that in Group 2 animals. These findings suggest that low-dose combination of CREE and UA is effective in the treatment of diabetes

Ursolic acid rich Ocimum sanctum L leaf extract loaded nanostructured lipid carriers ameliorate adjuvant induced arthritis in rats by inhibition of COX-1, COX-2, TNF-α and IL-1: Pharmacological and docking studies.

Ursolic acid (UA) is a promising molecule with anti-inflammatory, analgesic and potential anti-arthritic activity.This study was undertaken to make formulation and evaluation of Ocimum sanctum L. leaf extract (OLE) loaded nano-structured lipid carriers (OLE-NLCs) for improved transdermal delivery of UA. Different surfactants, solid lipids and liquid lipids were used for the preparation of NLCs. The NLCs were developed using emulsion solvent diffusion and evaporation method. Different physicochemical properties, entrapment efficacy, in vitro release evaluation, and ex vivo permeation studies of the prepared NLCs were carried out. The in vivo anti-arthritic activity of OLE-loaded NLC gel and control gel formulation (OLE free NLC gel) against Complete Freund's Adjuvant (CFA) induced arthritis in wister albino rats was also carried out.OLE-NLCs were composed of spherical particles having a mean particle size of ~120 nm, polydispersity index of ~0.162 and zeta potential of ~ -27 mV. The high entrapment efficiency (EE) of UA ~89.56% was attained. The in vitro release study demonstrated a prolonged release of UA from the NLCs up to 12 h. The developed formulation was found to be significantly better with respect to the drug permeation amount with an enhancement ratio of 2.69 as compared with marketed formulation. The in vivo biological activity investigations, studies showed that the newly prepared NLCs formulation of OLE showed excellent anti-arthritic activity and the results were found at par with standard marketed diclofenac gel for its analgesic and anti-arthritic activities. These results were also supported by radiological analysis and molecular docking studies.The overall results proved that the prepared OLE-NLCs were very effective for the treatment of arthritis and the results were found at par with standard marketed the standard formulation of diclofenac gel

Comparative Biochemical and Histopathological Studies on the Efficacy of Metformin and Virgin Olive Oil against Streptozotocin-Induced Diabetes in Sprague-Dawley Rats

Treatment of diabetic patients with antioxidant, such as extra virgin olive oil (EVOO), may be beneficial in numerous debilitating complexities. This study was aimed at assessing the protective role of virgin olive oil in reducing hyperglycemia in streptozotocin- (STZ-) induced diabetic rats. Thirty-six healthy male Sprague-Dawley rats were divided into six groups (6 rats per group) including nondiabetic control (NC), diabetic control (DC), and animals treated with metformin, olive oil, and a combination of olive oil and metformin, respectively. The protective effect of olive oil was evaluated by determining the biochemical parameters (lipid profile, liver, and kidney) and by studying the histopathological alterations in pancreas, liver, and kidney tissues. The results showed a significant increase in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels in diabetic rats. ALP levels remained significantly elevated in the diabetic rats that were treated with metformin and/or olive oil, and the highest level was noted in the group treated with olive oil (568.33 U/L). Contrarily, pretreatment with olive oil significantly decreased ALT (67.64 U/L) and ALP (226.17 U/L) levels. Histopathological data revealed that all the disorganized islets of Langerhans along with the clusters of inflammatory cells were absent in the group pretreated with the combination of virgin olive oil and metformin, which shows that prophylactic administration of this combination reduces the diabetic complications in a much better way. Therefore, pretreatment with olive oil with or without metformin is an encouraging approach for diabetes therapy with immense potential

Effect of Vitamin K on Bone Mineral Density and Fracture Risk in Adults: Systematic Review and Meta-Analysis

Summary: Recent studies have proposed that adequate intake of Vitamin K (VK) is associated with a low risk of fracture and high bone mineral density (BMD) to improve skeletal health in adults. This systematic review was designed to summarize the most relevant and updated evidence discussing the relationship between VK and bone. It explores the effect of VK deficiency and its supplementation on various bone parameters. Methods: The distinct databases such as PubMed, the Cochrane Library, Google Scholar, National Clinical Trials, Current Controlled Trials, and Clinical Trials were searched up to Jan 2020 to identify eligible trials. All relevant randomized controlled trial studies with any oral dosage form of VK supplement administered for at least six months and assessing BMD or fracture in adults were extracted. Finally, two independent reviewers identified 20 relevant citations for the systematic review and extracted data in tabular form. Results: The meta-analysis was performed with all studies, including postmenopausal and osteoporotic females, for both total clinical and vertebral fracture outcomes. The quantitative analysis showed that the odds ratios (OR) of any fracture were lower for VK as compared to control [OR 0.42 (95% CI 0.27 to 0.66)] for vertebral fractures and OR of 0.44 (95% CI 0.23 to 0.88) for clinical fracture. For the BMD, a meta-analysis of the pooled effect of interventional studies suggested a non-significant association between the use of VK and improvement in femoral BMD (CI 95%, p = 0.08 [&minus;0.03&ndash;0.20]). Conclusion: VK decreases general fracture risk, and it can be an option to counter bone loss disorders. However, insufficient evidence is available regarding the significant impact of VK on femoral neck BMD. Therefore, further studies are required to establish the therapeutic value of VK as a treatment for osteoporosis

Medicinal Plants and Related Ethnomedicinal Knowledge in the Communities of Khadukhel Tehsil, Buner District, Pakistan

The local communities of Pakistan have vast traditional knowledge about local medicinal plants that is centuries old and transferred from generation to generation, but now, the survival of this precious ethnic knowledge is threatened. This study aimed to document the ethnomedicinal information residing within the communities of the Khadukhel Tehsil, Buner District, Pakistan. To conserve this valuable traditional knowledge, data were collected through a semi-structured questionnaire, one-on-one interviews, and group discussions. From 2018 to 2021, 853 people were interviewed regarding 317 plant species. Most of the ethnomedicinal data were obtained from members of the 60&ndash;69 age group. The most dominant plant family was Asteraceae (27 sp.). Leaves (124 sp.) were the most dominant plant part used in medicines, and paste (80 sp.) was the most common herbal formulation method. Most (88) medicinal plants were used to cure digestive system diseases. The collected medicinal plants and related indigenous medicinal knowledge were compared with previously published work on the surrounding areas. We suggest a phytochemical and pharmacological evaluation of the collected medicinal plants for the discovery of new drugs

Molecular interactions of <i>Ursolic acid</i> (Blue ball and stick) with Cox-2 (Red Cartoon/Surface).

<p>Molecular interactions of <i>Ursolic acid</i> (Blue ball and stick) with Cox-2 (Red Cartoon/Surface).</p

Effect of OLE loaded NLC gel in CFA induced arthritic rats (X-ray photographs).

<p>A: Group-I. Normal control; B: Group-II. Toxic control; C: Group-III. OLE loaded NLC gel; D: Group-IV. Marketed gel.</p