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1.
A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract "Fenfuro®" in Type 2 Diabetics.
Hota, D, Padhy, BM, Maiti, R, Bisoi, D, Sahoo, JP, Patro, BK, Kumar, P, Goel, A, Banik, SP, Chakraborty, S, et al
Journal of the American Nutrition Association. 2024;(2):147-156
Abstract
BACKGROUND Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.
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2.
Revisiting the Multifaceted Therapeutic Potential of Withaferin A (WA), a Novel Steroidal Lactone, W-ferinAmax Ashwagandha, from Withania Somnifera (L) Dunal.
Kumar, P, Banik, SP, Goel, A, Chakraborty, S, Bagchi, M, Bagchi, D
Journal of the American Nutrition Association. 2024;(2):115-130
Abstract
Withania somnifera (L.) Dunal, abundant in the Indian subcontinent as Ashwagandha or winter cherry, is a herb of unprecedented therapeutic value. The number of ailments for which crude Ashwagandha extract can be used as a preventive or curative is practically limitless; and this explains why its use has been in vogue in ancient Ayurveda since at-least about four thousand years. The therapeutic potential of Ashwagandha mainly owes from its reservoir of alkaloids (isopelletierine, anaferine), steroidal lactones (withanolides) and saponins with an extra acyl group (sitoindoside VII and VIII). Withaferin A is an exceptionally potent withanolide which is found in high concentrations in W. somnifera plant extracts. The high reactivity of Withaferin A owes to the presence of a C-28 ergostane network with multiple sites of unsaturation and differential oxygenation. It interacts with the effectors of multiple signaling pathways involved in inflammatory response, oxidative stress response, cell cycle regulation and synaptic transmission and has been found to be significantly effective in inducing programmed cell death in cancer cells, restoring cognitive health, managing diabetes, alleviating metabolic disorders, and rejuvenating the overall body homeostasis. Additionally, recent studies suggest that Withaferin A (WA) has the potential to prevent viral endocytosis by sequestering TMPRSS2, the host transmembrane protease, without altering ACE-2 expression. The scope of performing subtle structural modifications in this multi-ring compound is believed to further expand its pharmacotherapeutic horizon. Very recently, a novel, heavy metal and pesticide free formulation of Ashwagandha whole herb extract, with a significant amount of WA, termed W-ferinAmax Ashwagandha, has been developed. The present review attempts to fathom the present and future of this wonder molecule with comprehensive discussion on its therapeutic potential, safety and toxicity.Key teaching pointsWithania somnifera (L.) Dunal is a medicinal plant with versatile therapeutic values.The therapeutic potential of the plant owes to the presence of withanolides such as Withaferin A.Withaferin A is a C-28 ergostane based triterpenoid with multiple reactive sites of therapeutic potential.It is effective against a broad spectrum of ailments including neurodegenerative disorders, cancer, inflammatory and oxidative stress disorders and it also promotes cardiovascular and sexual health.W-ferinAmax Ashwagandha, is a heavy metal and pesticide free Ashwagandha whole herb extract based formulation with significant amount of Withaferin A.
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3.
Therapeutic potential of tocotrienols as chemosensitizers in cancer therapy.
Sailo, BL, Chauhan, S, Hegde, M, Girisa, S, Alqahtani, MS, Abbas, M, Goel, A, Sethi, G, Kunnumakkara, AB
Phytotherapy research : PTR. 2024
Abstract
Chemoresistance is the adaptation of cancer cells against therapeutic agents. When exhibited by cancer cells, chemoresistance helps them to avoid apoptosis, cause relapse, and metastasize, making it challenging for chemotherapeutic agents to treat cancer. Various strategies like dosage modification of drugs, nanoparticle-based delivery of chemotherapeutics, antibody-drug conjugates, and so on are being used to target and reverse chemoresistance, one among such is combination therapy. It uses the combination of two or more therapeutic agents to reverse multidrug resistance and improve the effects of chemotherapy. Phytochemicals are known to exhibit chemosensitizing properties and are found to be effective against various cancers. Tocotrienols (T3) and tocopherols (T) are natural bioactive analogs of vitamin E, which exhibit important medicinal value and potential curative properties apart from serving as an antioxidant and nutrient supplement. Notably, T3 exhibits a variety of pharmacological activities like anticancer, anti-inflammatory, antiproliferative, and so on. The chemosensitizing property of tocotrienol is exhibited by modulating several signaling pathways and molecular targets involved in cancer cell survival, proliferation, invasion, migration, and metastasis like NF-κB, STATs, Akt/mTOR, Bax/Bcl-2, Wnt/β-catenin, and many more. T3 sensitizes cancer cells to chemotherapeutic drugs including cisplatin, doxorubicin, and paclitaxel increasing drug concentration and cytotoxicity. Discussed herewith are the chemosensitizing properties of tocotrienols on various cancer cell types when combined with various drugs and biological molecules.
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4.
The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options.
Deep, A, Swaroop, S, Dubey, D, Rawat, A, Verma, A, Baisya, B, Parihar, R, Goel, A, Rungta, S
Journal of molecular recognition : JMR. 2024;(1):e3066
Abstract
Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine-were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.
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5.
Andrographis Reverses Gemcitabine Resistance through Regulation of ERBB3 and Calcium Signaling Pathway in Pancreatic Ductal Adenocarcinoma.
Okuno, K, Xu, C, Pascual-Sabater, S, Tokunaga, M, Takayama, T, Han, H, Fillat, C, Kinugasa, Y, Goel, A
Biomedicines. 2023;(1)
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, primarily due to intrinsic or acquired resistance to chemotherapy, such as Gemcitabine (Gem). Naturally occurring botanicals, including Andrographis (Andro), can help enhance the anti-tumorigenic therapeutic efficacy of conventional chemotherapy through time-tested safety and cost-effectiveness. Accordingly, we hypothesized that Andro might reverse Gem resistance in PDAC. The critical regulatory pathways associated with Gem resistance in PDAC were identified by analyzing publicly available transcriptomic profiling and PDAC tissue specimens. A series of systematic in vitro experiments were performed using Gem-resistant (Gem-R) PDAC cells and patient-derived 3D-organoids to evaluate the Andro-mediated reversal of Gem resistance in PDAC. Transcriptomic profiling identified the calcium signaling pathway as a critical regulator of Gem-resistance (Fold enrichment: 2.8, p = 0.002). Within this pathway, high ERBB3 expression was significantly associated with poor prognosis in PDAC patients. The combination of Andro and Gem exhibited superior anti-cancer potential in Gem-R PDAC cells through potentiating cellular apoptosis. The combined treatment down-regulated ERBB3 and decreased intracellular calcium concentration in Gem-R PDAC cells. Finally, these findings were successfully interrogated in patient-derived 3D-organoids. In conclusion, we demonstrate novel evidence for Andro-mediated reversal of chemoresistance to Gem in PDAC cells through the regulation of ERBB3 and calcium signaling.
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6.
Efficacy of a Proprietary Fenugreek Seed Extract (Trigonella foenum-graecum, Furocyst®) in Women with Polycystic Ovary Syndrome (PCOS): a Randomized, Double-Blind, Placebo-Controlled Study.
Singh, A, Gainder, S, Banerjee, P, Goel, A, Kumar, P, Mondal, B, Banik, SP, Bagchi, D
Journal of the American Nutrition Association. 2023;(7):651-659
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia, a quite common heterogenous endocrine/hormonal disorder, and accompanied by elevated androgen level, menstrual irregularity, and hirsutism. The consequences include infertility or miscarriage. It is a challenging problem to the physicians. In a one-arm, non-randomized preliminary investigation in fifty premenopausal women, we demonstrated the efficacy of Furocyst®, a patented, standardized Trigonella foenum-graecum extract, in ameliorating the symptoms of PCOS over a period of 90 consecutive days. OBJECTIVE In the present study, a double-blind, two-arm, single-center, randomized, comparative study was conducted to assess the efficacy of Furocyst® (2 capsules of 500 mg/day) in 208 pre-menopausal women diagnosed with PCOS. METHODS Ethical committee approval was obtained. A total of 208 subjects (placebo = 95; Furocyst® = 113; age:18-45 years, BMI < 42 kg/m2) completed the investigation. The comparative efficacy of placebo and Furocyst® was assessed on the number of cysts, ovarian volume, hirsutism, LH:FSH ratio, titer of TSH, SHBG, prolactin and free testosterone. Key clinical parameters such as fasting blood glucose levels, HOMA Index, cholesterol, LDL, and triglyceride levels, as well as total blood chemistry were also investigated. RESULTS Furocyst® supplementation significantly reduced the number of cysts, ovarian volume, and hirsutism levels, as well as normalized the menstrual cycle in Furocyst®-treated subjects as compared to placebo group. Furocyst® significantly reduced luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and thyroid stimulating hormone (TSH) levels, and reduced the prolactin and SHBG levels. Furocyst® significantly reduced the fasting blood glucose levels, HOMA Index, cholesterol, LDL, and triglyceride levels as compared to the placebo group, while the free testosterone levels were significantly decreased in the Furocyst® group. CONCLUSION The studies collectively demonstrated the efficacy of Furocyst® as a safe, natural phytochemical-based formulation to alleviate the symptoms of PCOS. No significant adverse events were observed.
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7.
Pathogenesis of rheumatoid arthritis and its treatment with anti-inflammatory natural products.
Sharma, A, Goel, A
Molecular biology reports. 2023;(5):4687-4706
Abstract
Introduction Rheumatoid arthritis (RA) is a common autoimmune disease across the globe that is chronic and systemic as well. The disease is linked with autoantibodies and is inflammatory, eventually targeting several molecules along with certain modified self-epitopes. The disease majorly affects the joints of an individual. Rheumatoid arthritis is manifested clinically by polyarthritis linked with the dysfunction of the joints. This chiefly affects the synovial joint lining and is linked with progressive dysfunction, premature death, along with socioeconomic implications. The macrophage activation, along with the activation of certain defense cells, results in a response to self-epitopes that helps in providing a better understanding of the disease pathogenesis. Material and methodology For this review article, papers have been retrieved and reviewed from database including PubMed, Scopus and Web of science. Relevant papers were taken fulfilling the criteria for writing this review article. Results This has resulted in the establishment of several new therapeutic techniques that serve as potential inhibitors of such cells. Researchers have gained an interest in understanding this disease to provide strategies for treatment in the last two decades. This also includes recognition followed by the treatment of the disease at its early stages. Various allopathic treatment approaches often have chronic and toxic teratogenic effects. However, to avoid this issue of toxicity followed by side effects, certain medicinal plants have been used in treating RA. Conclusion Medicinal plants possess active phytoconstituents that entail antioxidants as well as anti-inflammatory properties, making them a helpful alternative to allopathic drugs that are often linked with highly toxic effects. This review paper entails a thorough discussion of the epidemiology, pathophysiology, diagnosis, and management of RA. The paper will also focus on the use of herbal plants in the treatment of the disease to avoid the side effects that generally occur in allopathic treatment.
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8.
Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma.
Miyazaki, K, Morine, Y, Xu, C, Nakasu, C, Wada, Y, Teraoku, H, Yamada, S, Saito, Y, Ikemoto, T, Shimada, M, et al
Cells. 2023;(4)
Abstract
Lenvatinib is a multi-kinase inhibitor approved as a first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate is unsatisfactory, primarily due to the acquisition of resistance, which limits its clinical significance for treating patients with HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and is considered an important therapeutic target in HCC. Curcumin, one of the most studied naturally occurring botanicals with robust anti-cancer activity, is also reported to be a potent tyrosine kinase inhibitor. In this study, we hypothesized that the anti-EGFR potential of Curcumin might help overcome Lenvatinib resistance in HCC. We established two Lenvatinib-resistant cells and discovered that a combination of Curcumin and Lenvatinib exhibited a synergistic anti-tumor efficacy in the resistant HCC cell lines. In line with previous reports, Lenvatinib-resistant cell lines revealed significant activation of the EGFR, and genomewide transcriptomic profiling analysis identified that the PI3K-AKT pathway was associated with Lenvatinib resistance. The combination treatment with Curcumin and Lenvatinib dramatically suppressed gene and protein expression of the EGFR-PI3K-AKT pathway, suggesting Curcumin overcomes Lenvatinib resistance via inhibition of EGFR. We further validated these findings in tumor spheroids derived from resistant cell lines. In conclusion, we, for the first time, report that Curcumin reverses Lenvatinib resistance in HCC, and that their combination has clinical application potential for adjunctive treatment in HCC.
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9.
SGLT2 inhibitors in hypertension: Role beyond diabetes and heart failure.
Gupta, R, Maitz, T, Egeler, D, Mehta, A, Nyaeme, M, Hajra, A, Goel, A, Sreenivasan, J, Patel, N, Aronow, WS
Trends in cardiovascular medicine. 2023;(8):479-486
Abstract
Type 2 Diabetes Mellitus (T2DM) is a pandemic that affects millions of patients worldwide. Diabetes affects multiple organ systems leading to comorbidities including hypertension. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) recently have been approved for the treatment of T2DM and heart failure with reduced and preserved ejection fraction. Retrospective analyses of clinical trials have noted SGLT2 inhibitors to have a promising effect on blood pressure. Moreover, the observed blood pressure reduction is not just an acute effect of treatment initiation but has been shown to have a long-term impact on both systolic and diastolic blood pressure. The mechanism of action leading to the blood pressure reduction is still unclear; however, proposed mechanisms are related to the natriuretic effect, modification of the renin-angiotensin-aldosterone system, and/or the reduction in the sympathetic nervous system, SGLT2i should be considered as second-line medication in those patients with diabetes or heart disease and concomitant hypertension. This article reviews the pharmacology, side effect profile, and clinical trials surrounding the use of SGLT2i for the treatment of hypertension.
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10.
Role of GSDM family members in airway epithelial cells of lung diseases: a systematic and comprehensive transcriptomic analysis.
Liu, X, Zhang, L, Zhu, B, Liu, Y, Li, L, Hou, J, Qian, M, Zheng, N, Zeng, Y, Chen, C, et al
Cell biology and toxicology. 2023;(6):2743-2760
Abstract
Gasdermin (GSDM) family, the key executioners of pyroptosis, play crucial roles in anti-pathogen and anti-tumor immunities, although little is known about the expression of GSDM in lung diseases at single-cell resolution, especially in lung epithelial cells. We comprehensively investigated the transcriptomic profiles of GSDM members in various lung tissues from healthy subjects or patients with different lung diseases at single cell level, e.g., chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), lung adenocarcinoma (LUAD), or systemic sclerosis (SSC). The expression of GSDM members varied among pulmonary cell types (immune cells, structural cells, and especially epithelial cells) and even across lung diseases. Regarding disease-associated specificities, we found that GSDMC or GSDMD altered significantly in ciliated epithelia of COPD or LUAD, GSDMD in mucous, club, and basal cells of LUAD and GSDMC in mucous epithelia of para-tumor tissue, as compared with the corresponding epithelia of other diseases. The phenomic specificity of GSDM in lung cancer subtypes was noticed by comparing with 15 non-pulmonary cancers and para-cancer samples. GSDM family gene expression changes were also observed in different lung epithelial cell lines (e.g., HBE, A549, H1299, SPC-1, or H460) in responses to external challenges, including lipopolysaccharide (LPS), lysophosphatidylcholine (lysoPC), cigarette smoking extract (CSE), cholesterol, and AR2 inhibitor at various doses or durations. GSDMA is rarely expressed in those cell lines, while GSDMB and GSDMC are significantly upregulated in human lung epithelia. Our data indicated that the heterogeneity of GSDM member expression exists at different cells, pathologic conditions, challenges, probably dependent upon cell biological phenomes, functions, and behaviors, upon cellular responses to external changes, and the nature and severity of lung disease. Thus, the deep exploration of GSDM phenomes may provide new insights into understanding the single-cell roles in the tissue, regulatory roles of the GSDM family in the pathogenesis, and potential values of biomarker identification and development.