PMID: 

Mol Cell Biochem. 2016 Feb ;413(1-2):109-18. Epub 2016 Jan 4. PMID: 26728998

Abstract Title: 

Galangin inhibits hypertrophic scar formation via ALK5/Smad2/3 signaling pathway.

Abstract: 

Hypertrophic scar (HS) is characterized by excessive fibrosis associated with aberrant function of fibroblasts. Currently, no satisfactory drug has been developed to treat the disease. Here we found that a flavonoid natural product, galangin, could significantly attenuate hypertrophic scar formation in a mechanical load-induced mouse model. Both in vivo and in vitro studies demonstrated that galangin remarkably inhibited collagen production, proliferation, and activation of fibroblasts. Besides, galangin suppressed the contractile ability of hypertrophic scar fibroblasts. Further Western blot analysis revealed that galangin dose-dependently down-regulated Smad2 and Smad3 phosphorylation. Such bioactivity of galangin resulted from its selective targeting to the activin receptor-like kinase 5 (ALK5) was demonstrated by ALK5 knockdown and over-expression experiments. Taken together, this compound could simultaneously inhibit both the accumulation of collagen and abnormal activation/proliferation of fibroblasts, which were the two pivotal factors for hypertrophic scar formation, thus suggesting that galangin serves as a potential agent for treatment of HS or other fibroproliferative disorders.

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PMID: 

Mol Med Rep. 2016 May ;13(5):4238-44. Epub 2016 Mar 24. PMID: 27035542

Abstract Title: 

Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal transition and inducing apoptosis in renal cell carcinoma.

Abstract: 

Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence, has been shown to have anticancer properties against several types of cancer cells. However, the influence of galangin on human renal cancer cells remains to be elucidated. In the present study, proliferation of 786‑0 and Caki‑1 cells was suppressed following exposure tovarious doses of galangin. Cell invasion and wound healing assays were used to observe the effect of galangin on invasion and migration. The results demonstrated that Galangin inhibited cell invasion by suppressing the epithelial mesenchymal transition (EMT), with an increase in the expression of E‑cadherin and decreased expression levels of N‑cadherin and vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The results revealed that galangin induced apoptosis in a dose‑dependent manner. The accumulation of reactive oxygen species (ROS) is an important contributing factor for the apoptosis of various types of cancer cell. The dichlorofluorescein-diacetate method was used to determine the level of ROS. Galangin induced the accumulation of intracellular ROS and malondialdehyde, and decreased the activities of total antioxidant and superoxide dismutase in renal cell carcinoma cells. Galangin exerted an antiproliferative effect and inhibited renal cell carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis, accompanied by the production of ROS. Therefore, the present data suggested that galangin may have beneficial effects by preventing renal cell carcinoma growth, inhibiting cell invasion via the EMT and inducing cell apoptosis.

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PMID: 

Sci Rep. 2016 07 27 ;6:30496. Epub 2016 Jul 27. PMID: 27460655

Abstract Title: 

Galangin Induces Autophagy via Deacetylation of LC3 by SIRT1 in HepG2 Cells.

Abstract: 

Galangin suppresses proliferation and induces apoptosis and autophagy in hepatocellular carcinoma (HCC) cells, but the precise mechanism is not clear. In this study, we demonstrated that galangin induced autophagy, enhanced the binding of SIRT1-LC3 and reduced the acetylation of endogenous LC3 in HepG2 cells. But this autophagy was inhibited by inactivation of SIRT1 meanwhile, galangin failed to reduce the acetylation of endogenous LC3 after SIRT1 was knocked-down. Collectively, these findings demonstrate a new mechanism by which galangin induces autophagy via the deacetylation of endogenous LC3 by SIRT1.

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Dr. Fauci, whose guidance to President Trump has resulted in a near total lockdown of the country, recently published an editorial in New England Journal of Medicine that rightly points out serious flaws in his own doom-and-gloom COVID-19 fatality projections.

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PMID: 

Neurochem Res. 2011 Feb ;36(2):250-7. Epub 2010 Nov 13. PMID: 21076869

Abstract Title: 

Effects of Melissa officinalis L. (lemon balm) extract on neurogenesis associated with serum corticosterone and GABA in the mouse dentate gyrus.

Abstract: 

Lemon balm, leaves of Melissa officinalis L., has been used for anti-anxiety and spasmolytics. We observed the extract of Melissa officinalis L. (MOE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of middle-aged mice (12 months of age) using Ki67 and doublecortin (DCX), respectively. We also observed changes in corticosterone, GAD67 and GABA-transaminase (GABA-T) to check their possible mechanisms related to neurogenesis. We administered 50 or 200 mg/kg MOE to the animals once a day for 3 weeks. For labeling of newly generated cells, we also administered 5-bromodeoxyuridine (BrdU) twice a day for 3 days from the day of the first MOE treatment. Administration of 50 or 200 mg/kg MOE dose-dependently increased Ki67 positive nuclei to 244.1 and 763.9% of the vehicle-treated group, respectively. In addition, 50 or 200 mg/kg MOE significantly increased DCX positive neuroblasts with well-developed (tertiary) dendrites. Furthermore, MOE administration significantly increased BrdU/calbindin D-28 k double labeled cells (integrated neurons into granule cells in the DG) to 245.2% of the vehicle-treated group. On the other hand, administration of MOE reduced corticosterone levels in serum and decreased GABA-T levels in the DG homogenates. These results suggest that MOE increases cell proliferation, neuroblast differentiation and integration into granule cells by decreasing serum corticosterone levels as well as by increasing GABA levels in the mouse DG.

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PMID: 

Med Princ Pract. 2014 ;23(4):340-5. Epub 2014 Jun 18. PMID: 24942615

Abstract Title: 

Efficacy of Melissa officinalis in suppressing ventricular arrhythmias following ischemia-reperfusion of the heart: a comparison with amiodarone.

Abstract: 

OBJECTIVE: We aimed to assess the influence of Melissa officinalis (lemon balm), a well-known herbal drug with numerous applications in traditional and modern medicine, on cardiac conduction and susceptibility to lethal ventricular arrhythmia.MATERIALS AND METHODS: Forty-two male Wistar rats were divided into a control group (CTL), an M. officinalis group that received the aqueous extract of M. officinalis L. intraperitoneally (i.p.) at dosages of 50, 100, 200 and 400 mg/ml/kg, respectively, and an amiodarone group (Amio group) that received 30 mg/ml/kg i.p. of amiodarone. Heart ischemia/reperfusion was induced by the ligation and release of the left anterior descending branch of the left coronary artery.RESULTS: There were no statistical differences between the groups in the basal heart rate and blood pressure. PR, corrected QT (QTc) and QRS intervals increased in the M. officinalis and Amio groups. PR and QTc were statistically significant only in the Amio group and QRS was significant only in the group receiving 400 mg of M. officinalis (M400 group) in comparison with the CTL group. During the reperfusion period, the decrease in ventricular fibrillations was statistically significant in all groups (except the M400 group) when compared with the CTL group. The score of arrhythmia severity also decreased, but was statistically significant only in the Amio group (p

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PMID: 

J Ethnopharmacol. 2016 Feb 3 ;178:238-50. Epub 2015 Dec 15. PMID: 26702505

Abstract Title: 

The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6J mice.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from M. officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy.MATERIALS AND METHODS: ALS-L1023 was prepared by a two-step organic solvent fractionation from M. officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches.RESULTS: ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice.CONCLUSIONS: These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.

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PMID: 

PLoS One. 2015 ;10(5):e0126422. Epub 2015 May 15. PMID: 25978046

Abstract Title: 

Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial.

Abstract: 

The aim of this study was to evaluate the safety, tolerability and pharmacokinetics of single dose of Melissa officinalis extract which contained rosmarinic acid, including food-effects in healthy individuals. A total of eleven healthy individuals were randomly assigned to treatment arms in the two studies [Study 1 (fasted state) and Study 2 (fed state)]. Rosmarinic acid in serum was measured by a coulometric detection method using High-Performance Liquid Chromatography electrochemical detector. The serum concentration of total rosmarinic acid peaked at 1 hour after administration of Melissa officinalis extract containing 500mg rosmarinic acid in fasted state, with a maximum serum concentration 162.20 nmol/ L. The area under the curve for intact rosmarinic acid was calculated from the serum concentration-time profile to be 832.13 nmol• hour/ L. Food intake increases area under the curve and delayed time at which the maximum serum concentration. Rosmarinic acid supplementation did not affect liver, kidney, or blood cell function parameters. No adverse event was reported by any of the participants due to the study treatment. Single dose of Melissa officinalis extract containing 500 mg rosmarinic acid appears to be safe and tolerable in healthy individuals. Food intake increased the exposure of rosmarinic acid and delayed absorption of rosmarinic acid in healthy individuals.

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PMID: 

Mol Nutr Food Res. 2019 09 ;63(17):e1900403. Epub 2019 Jun 25. PMID: 31206248

Abstract Title: 

A Two-Week Treatment with Plant Extracts Changes Gut Microbiota, Caecum Metabolome, and Markers of Lipid Metabolism in ob/ob Mice.

Abstract: 

SCOPE: Targeting gut microbiota dysbiosis by prebiotics is effective, though side effects such as abdominal bloating and flatulence may arise following high prebiotic consumption over weeks. The aim is therefore to optimize the current protocol for prebiotic use.METHODS AND RESULTS: To examine the prebiotic properties of plant extracts, two independent studies are conducted in ob/ob mice, over two weeks. In the first study, Porphyra umbilicalis and Melissa officinalis L. extracts are evaluated; in the second study, a high vs low dose of an Emblica officinalis Gaertn extract is assessed. These plant extracts affect gut microbiota, caecum metabolome, and induce a significant lower plasma triacylglycerols (TG) following treatment with P. umbilicalis and significantly higher plasma free fatty acids (FFA) following treatment with the low-dose of E. officinalis Gaertn. Glucose- and insulin-tolerance are not affected but white adipose tissue and liver gene expression are modified. In the first study, IL-6 hepatic gene expression is significantly (adjusted p = 0.0015) and positively (r = 0.80) correlated with the bacterial order Clostridiales in all mice.CONCLUSION: The data show that a two-week treatment with plant extracts affects the dysbiotic gut microbiota and changes both caecum metabolome and markers of lipid metabolism in ob/ob mice.

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PMID: 

J Complement Integr Med. 2019 Jan 25 ;16(3). Epub 2019 Jan 25. PMID: 30681971

Abstract Title: 

The effects of a Melissa officinalis L. based product on metabolic parameters in patients with type 2 diabetes mellitus: A randomized double-blinded controlled clinical trial.

Abstract: 

Background Diabetic patients are at increased risk for coronary artery disease. Since phytotherapy has been greatly common, finding safe and effective treatments is of importance. This study aimed to evaluate the effects of a Melissa officinalis L. based product (MO) in patients with type 2 diabetes. Methods A randomized double-blinded controlled study was conducted with 37 dyslipidemic diabetic patients, assigned to either MO or placebo (P) groups receiving two 500 mg capsules daily for 3 months. Finally, 32 cases completed the study and were included in the analysis; MO (n=16) and P (n=16). Results Safe and significant effects in terms of decreasing the serum level of triglyceride (TG) in all patients after 2 months (p-value=0.02) and in patients with higher baseline serum levels of TG (TG≥200 mg/dl) after 3 months (p-value=0.04) were shown in the MO group. However, no metabolic significant changes were seen compared to the control group. Significant decrease in both systolic and diastolic blood pressure from baseline values were also found in patients with higher systolic bloodpressure (SBP≥130 mmHg) (p-value=0.02) and those with higher diastolic blood pressure (DBP≥85 mmHg) (p-value=0.02) in the MO group. Conclusion This study showed that MO might be safe and beneficial in decreasing the serum TG level in dyslipidemic diabetic patients. Although, larger long-term studies are required.

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