PMID: 

Med Acupunct. 2020 Feb 1 ;32(1):24-28. Epub 2020 Feb 3. PMID: 32104524

Abstract Title: 

Acupuncture Treatment in Patients with Chronic Subjective Tinnitus: A Prospective, Randomized Study.

Abstract: 

This study investigated the effect, onset, duration of action, and short-term outcomes of acupuncture therapy for treating patients with severe chronic subjective tinnitus.This randomized controlled trial evaluated patients with chronic, idiopathic, and severe tinnitus. A total of 105 participants were divided into 2 groups using a randomization method: a study group who received verum acupuncture therapy ( = 53) and a sham acupuncture group ( = 52). Ten acupuncture sessions were given over 5 weeks. After treatment, each participant was monitored for up to 3 months according to changes on a visual analogue Scale (VAS), and Tinnitus Handicap Inventory (THI), and Pure-Tone Audiometry and Speech Discrimination (Interacoustics AC-40, Denmark) scores.The VAS and THI scores were evaluated. A statistically significant difference was noted between the sham and verum acupuncture groups at post-treatment follow-up ( 

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PMID: 

Microorganisms. 2020 Feb 6 ;8(2). Epub 2020 Feb 6. PMID: 32041173

Abstract Title: 

Effect of Dose and Timing of Burdock () Root Intake on Intestinal Microbiota of Mice.

Abstract: 

Water-soluble dietary fiber such as inulin improves the beta diversity of the intestinal microbiota of mice fed with a high-fat diet (HFD). The circadian clock is the system that regulates the internal daily rhythm, and it affects the pattern of beta diversity in mouse intestinal microbiota. Burdock () root contains a high concentration of inulin/fructan (approximately 50%) and is a very popular vegetable in Japan.also contains functional substances that may affect intestinal microbiota, such as polyphenols. We compared the effects of inulin andpowder on the diversity of the intestinal microbiota of HFD-fed mice. 16S rDNA from the intestinal microbiota obtained from feces was analyzed by 16S Metagenomic Sequencing Library Preparation. It was found to have a stronger effect on microbiota than inulin alone, suggesting that inulin has an additive and/or synergic action with other molecules inroot. We examined the effects of intake timing (breakfast or dinner) ofon intestinal microbiota. The intake ofroot in the evening had a stronger effect on microbiota diversity in comparison to morning intake. Therefore, it is suggested that habitual consumption ofroot in the evening may aid the maintenance of healthy intestinal microbiota.

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PMID: 

Food Chem Toxicol. 2019 Feb ;124:1-9. Epub 2018 Nov 24. PMID: 30481570

Abstract Title: 

Clinopodium vulgare L. (wild basil) extract and its active constituents modulate cyclooxygenase-2 expression in neutrophils.

Abstract: 

Clinopodium vulgare L. (wild basil) has a wide range of ethnopharmacological applications and accumulates a broad spectrum of phenolic compounds, recognized for their anti-inflammatory and anticancer properties. The triggered cyclooxygenase-2 (COX-2) expression is creating an immunosuppressive microenvironment in the inflamed tissue and considered to be the main cause of failure of even new anticancer-/immune-therapies. Nowadays, selective and novel plant-derived COX-2 inhibitors with safe profile are subject of profound research interest. This study aimed to analyze the metabolic profile of C. vulgare and search for phenolic molecules with potential biological properties. By application ofH and 2D-NMR (Nuclear Magnetic Resonance) profiling, caffeic, chlorogenic acids and catechin were identified along with a bunch of primary and secondary metabolites. Further, the biological effect of C. vulgare extract (CVE) and its constituents on zymosan-induced COX-2 expression and apoptosis of murine neutrophils have been studied. The CVE, caffeic and chlorogenic acids inhibited zymosan-induced COX-2 expression in bone marrow neutrophils, in vitro and in vivo activated. The obtained data indicate that CVE may have a good potential to manipulate neutrophil functions, however, its action may depend on the cellular state, the inflammatory milieu and the relative content of caffeic and chlorogenic acid in the extract.

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PMID: 

Mater Sociomed. 2019 Dec ;31(4):236-240. PMID: 32082085

Abstract Title: 

Renoprotective Effect of Ocimum Basilicum (Basil) Against Diabetes-induced Renal Affection in Albino Rats.

Abstract: 

Introduction: Diabetic nephropathy is the second most common secondary type of glomerular diseases among Saudi patients after systemic lupus erythematosus.() was reported to have anti-diabetic and antioxidants effects.Aim: This study aimed to evaluate the efficacy ofin controlling STZ-induced diabetes mellitus in rats and preserving the structure of kidney against diabetes-induced nephropathy.Methods: This study utilized forty adult male Spraque-Dawley rats assigned into four groups (n=10 each); control, streptozotocin-induced diabetic, metformin-treated and-treated groups. The blood glucose level (BGL), total anti-oxidant capacity (TAC), serum creatinine and BUN levels were assessed. Kidneys were dissected out and processed for histopathological and immunohistochemical assessment.Results: The BGL significantly decreased in Metformin- and-treated (p=0.02, p=0.01) rats while TAC significantly increased (p=0.01, p=0.003) respectively, compared to the untreated diabetic rats. In addition,significantly reduced (p=0.004, p=0.02) both creatinine and BUN levels compared to the untreated diabetic group, respectively. Examination of kidney of-treated diabetic rats revealed few degenerated renal tubules, with no inflammatory cell infiltrates, peritubular capillaries congestion and minimal peritubular collagen fibers deposition. It also reduced immunoexpression of desmin andαsmooth muscle actin in glomeruli of-treated diabetic rats.Conclusion: Glucose lowering and antioxidant effects ofwas evident biochemically in this study.could protect the kidney against diabetes-induced nephropathy as revealed biochemically and histopathologically. Further exploration of the mechanism and assessment of efficacy in human through clinical study are recommended.

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PMID: 

Molecules. 2020 Feb 14 ;25(4). Epub 2020 Feb 14. PMID: 32075047

Abstract Title: 

Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin.

Abstract: 

Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure.

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PMID: 

Phytomedicine. 2020 Feb 15 ;68:153186. Epub 2020 Feb 15. PMID: 32088353

Abstract Title: 

Rosmarinic acid exerts an anticancer effect on osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway.

Abstract: 

BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor. This disease has exhibited a progressively lower survival rate over the past several decades, which has resulted in it becoming a main cause of death in humans. Rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts powerful anticancer effects against multiple types of cancer; however, its potential effects on osteosarcoma remain unknown. Hence, the present study investigated the efficacy of RA against osteosarcoma and aimed to clarify the mechanisms underlying this process.METHODS: The effects of RA on cell viability, apoptosis, cell cycle distribution, migration, invasion, and signaling molecules were analyzed by CCK-8 assay, flowcytometric analysis, wound healing assay, Transwell assay, proteomic analysis, and use of shRNAs.RESULTS: RA exerted anti-proliferation and pro-apoptotic effects on U2OS and MG63 osteosarcoma cells. Apoptosis was induced via extrinsic and intrinsic pathways by increasing the Bax/Bcl-2 ratio, triggering the intracellular production of reactive oxygen species (ROS), reducing the mitochondrial membrane potential (MMP), and upregulating the cleavage rates of caspase-8, caspase-9, and caspase-3. Additionally, RA suppressed the migration and invasion of osteosarcoma cells by inhibiting the expression levels of matrix metalloproteinase-2 and -9 (MMP-2 and -9), which are associated with a weakening of the epithelial-mesenchymal transition (EMT). Moreover, proteomic analyses identified DJ-1 as a potential target for RA. Several studies have indicated an oncogenic role for DJ-1 using knockdowns via the lentiviral-mediated transfection of shRNA, which caused the conspicuous suppression of cell proliferation, migration, and invasion as well as the arrest of cell cycle progression. At the molecular level, the expression levels of DJ-1, p-PI3K, and p-Akt were reduced, whereas the protein levels of phosphatase and tensin homologue (PTEN) were increased.CONCLUSION: In conjunction with the high levels of DJ-1 expression in osteosarcoma tissues and cell lines, the present results suggested that RA exhibited anticancer effects in osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway. Therefore, DJ-1 might be a biological target for RA in osteosarcoma cells.

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PMID: 

Drug Discov Ther. 2018 ;12(3):133-141. PMID: 29998994

Abstract Title: 

Effects of Piper betle fractionated extracts on inhibition of Streptococcus mutans and Streptococcus intermedius.

Abstract: 

The overgrowth of certain strains of normal flora in oral cavity can cause many kinds of oral infections or diseases such as carries, periodontitis, and gingivitis. Prevention and treatment of these diseases are usually achieved by chemical antiseptics. However, these chemicals are found as negative impacts of human health hazards and accession of microbial resistance. The present study explores the potential of Piper betle extracts on inhibition of two oral pathogenic bacteria; Streptococcus mutans DMST 41283 and Streptococcus intermedius DMST 42700. P. betle demonstrated significantly higher inhibitory activity against both pathogenic strains than Acacia catechu, Camellia sinensis, Coccinia grandis, Solanum indicum, and Streblus asper. Among fractionated extracts of P. betle from several solvents, the extract from ethyl acetate (Pb-EtOAc) possessed the widest inhibition zone of 11.0± 0.1 and 11.3 ± 0.4 mm against both bacterial strains, respectively. Pb-EtOAc showed the same minimum inhibitory concentration of 0.5 mg/mL against both strains, whereas its minimum bactericidal concentrations were 2.0 and 0.5 mg/mL against S. mutans and S. intermedius, respectively. HPLC analysis demonstrated that the major active compound of Pb-EtOAc was 4-allylpyrocatechol. It was found that the killing kinetics of Pb-EtOAc against both test strains were time and dose dependent. Scanning electron microscopy micrographs showed the morphological changes and depletion of the tested pathogens indicating cell destruction after exposure to Pb-EtOAc. It is confirmed that Pb-EtOAc is potentially effective against both oral pathogens and might be used as natural alternative agents in prevention and treatment of oral infections caused by oral pathogenic bacteria.

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PMID: 

Biochem Pharmacol. 2019 Aug ;166:274-291. Epub 2019 May 31. PMID: 31154000

Abstract Title: 

Hydroxychavicol from Piper betle induces apoptosis, cell cycle arrest, and inhibits epithelial-mesenchymal transition in pancreatic cancer cells.

Abstract: 

Pancreatic cancer is a major cause of cancer-related mortality around the world. Currently, options for diagnosis and treatment are extremely limited, which culminates in a very high mortality rate. Intensive research spanning more than four decades has met several roadblocks in terms of improvement in overall survival. In this study, we have evaluated the effect of Hydroxychavicol (HC), a naturally occurring and abundantly isolatable allylarene from Piper betle leaves on pancreatic cancer cells. Our investigation reveals that HC inhibits proliferation and epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. HC induces DNA damage, as evidenced byγ-H2AX, 53BP1 induction and comet assay, which further results in mitotic catastrophe and apoptosis. The apoptosis induced by HC is JNK pathway-dependent and caspase-mediated. HC also inhibits migration and invasion of pancreatic cancer cells via a generalized repression of genes involved in EMT. Aquantitative real time PCR-based array revealed at least 14 different genes to be differentially expressed upon HC treatment in pancreatic cancer cells. These results show significant potential of HC as an anticancer agent against pancreatic cancer.

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PMID: 

Heliyon. 2020 Jan ;6(1):e03041. Epub 2019 Dec 26. PMID: 31909246

Abstract Title: 

Strengthening antioxidant defense&cardio protection by: An in-vitro study.

Abstract: 

Introduction: The purpose of this research work was to evaluateethyl acetate extract (PBEA) for its free radical scavenging, antioxidant, anti-apoptotic activities and its role in protecting against oxidative cardiac cell injury.Methods: The Free radical scavenging activity and antioxidant potential of PBEA were evaluated using various non-cellular methods (1,1-Diphenyl-2-picrylhydrazyl,β-carotene bleaching, superoxide anion, hydroxyl radical, hydrogen peroxideReducing power, Total phenolics and Total flavonoids). PBEA was standardized with Eugenol by GC-FID analysis. Furthermore, PBEA was also assessed for its cytotoprotective effect against 100μM HOin H9c2 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Intracellular reactive oxygen species scavenging and anti-apoptoic activity of PBEA was assessed by using 2', 7'-Dichlorofluorescein diacetate and Annexin- Propidium Iodide, respectively.Results: PBEA exhibited radical scavenging and antioxidant defense response at different magnitudes of potency. Eugenol, a cardiac protective bioactive molecule in PBEA was found to be 43.43± 1.46 mg/g of PBEA extract. Further, pre-incubation of H9c2 cells with 10 μg/ml PBEA for 24 h exhibited remarkable cytoprotective effect against HOinduced oxidative stress. PBEA at 10μg/ml dose with 24 h contact with H9c2 cells significantly enhanced the activity of cellular defense system and significantly decreased intracellular ROS (P

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PMID: 

J Oral Maxillofac Pathol. 2019 Sep-Dec;23(3):333-337. PMID: 31942110

Abstract Title: 

Antifungal activity of solvent extracts ofandLinn on: Ancomparative study.

Abstract: 

Background: Oral candidiasis is a common fungal infection caused by. In recent years,species have shown resistance against many synthetic drugs, which has highlighted the need for novel antifungal drugs with fewer side effects for effective management of candidiasis. Several studies have suggested that some plant species possess promising antimicrobial compounds.andLinn are such common medicinal plants that show strong antimicrobial activity by the release of secondary metabolites. However, the effect of these plants on oral candidiasis has not been studied and hence, the present study aimed to evaluate the antifungal activity of these plant extracts on the subcultures ofand compared with a standard drug, fluconazole.Materials and Methods: Subcultures ofobtained from oral thrush patients were used in the present study. Ethanolic and ethyl acetate extracts of(betel) andL. (tulsi) leaves were prepared by cold extraction method. The anticandidal activity and minimum inhibitory concentration (MIC) were evaluated using disc diffusion method and microbroth dilution method, respectively. Values were compared with the standard drug fluconazole.Results: Both the extracts exhibited anticandidal activity on the subcultures of. The ethyl acetate extract of mature betel leaf showed a maximum zone of inhibition (26 mm) when compared with tulsi and fluconazole (13 mm). Betel leaf extract showed better MIC values (125μg/ml) than tulsi (2000 μg/ml). However, these values were high when compared with those of fluconazole (62.5 μg/ml).Conclusion: Ethyl acetate extract of mature betel leaf exhibited good anticandidal activity than that of tulsi and fluconazole.

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