PMID: 

Med Hypotheses. 2019 Nov 27 ;136:109513. Epub 2019 Nov 27. PMID: 31812013

Abstract Title: 

Could PCSK9 be a new therapeutic target of Eugenol? In vitro and in silico evaluation of hypothesis.

Abstract: 

PCSK9 (Proprotein convertase Subtilisin/Kexin Type 9), an important regulator of lipid metabolism, has been shown to play a role in hepatocellular carcinoma by promoting metastasis. PCSK9 interferes with LDL metabolism and causes dyslipidemias in hematological malignancies particularly acute lymphoblastic leukemia. Nutraceuticals like berberine, curcumin and polydatin have been found effective in modulating PCSK9 expression by lowering LDL levels. Eugenol, a nutraceutical has shown a promising role in cancer due to its antioxidant and antihypercholesterolemic effects. In the present study, PCSK9 expression was measured in acute lymphoblastic leukemia (ALL) patients and was found to be significantly induced. Based on the results of expression analysis, a plausible hypothesis was made. Eugenol being an antioxidant will prevent oxidation of LDL. In the absence of ox-LDL, LOX1 scavenger receptor, which regulates PCSK9 expression, will not be activated. As the circulating LDL is reduced, it will no longer be able to support leukemia cell growth. The hypothesis was validated by an in silico and in vitro study. Molecular docking revealed hydrophobic interactions between ligand eugenol and macromolecules PCSK9 and LOX1. Expression of both PCSK9 and LOX1 were significantly reduced by eugenol in Jurkat cells. To conclude, PCSK9 could therapeutically be targeted by eugenol in leukemia cells.

read more

PMID: 

Cell Mol Neurobiol. 2019 Dec 11. Epub 2019 Dec 11. PMID: 31828466

Abstract Title: 

Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells.

Abstract: 

Neurodegenerative diseases all share several common features such as involvement of oxidative damage and mitochondrial dysfunction in pathogenesis. Oxidative stress induced by overproduction of mitochondrial reactive oxygen species (ROS) or impairment of the antioxidant deficiency results in mitochondrial dysfunction and initiation of the cell death cascade. Berberine (BBR), a traditional Chinese medicine, has been reported to exert anti-oxidative stress and anti-apoptosis effect in CNS diseases. However, the mechanism of BBR on regulating mitophagy and protecting mitochondrial function under oxidative stress remains unclear. In present study, we evaluated the beneficial effects of BBR on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity. Furthermore, we explored the protective role of BBR in mitochondrial function and mitophagy under oxidative stress in PC-12 cells. Our results demonstrated that BBR effectively inhibited t-BHP-induced apoptosis which is associated with the decreased leakage of lactate dehydrogenase (LDH) and ROS overproduction. Moreover, BBR significantly suppressed cytochrome c expression, upregulated the ratio of Bcl-2/Bax, and ameliorated mitochondrial dysfunction by optimizing mitochondria membrane potential (ΔΨm) status and ATP production. In addition, BBR reduced the expression of autophagy-specific marker LC3, SQTM1/p62, and maintained lysosome normal function which involved the restoration of upstream signaling pathway AKT and mTOR phosphorylation level. Collectively, these findings suggested thatBBR protects PC-12 cells from oxidative injury through inhibiting ROS level, mitochondria dysfunction, and mitophagy via PI3K/AKT/mTOR signaling pathways, which suggest a potential therapeutic strategy for oxidative stress and neurotoxic damages.

read more

PMID: 

PLoS One. 2019 ;14(12):e0225660. Epub 2019 Dec 16. PMID: 31841506

Abstract Title: 

Combination treatment of berberine and solid lipid curcumin particles increased cell death and inhibited PI3K/Akt/mTOR pathway of human cultured glioblastoma cells more effectively than did individual treatments.

Abstract: 

The treatment of glioblastoma is challenging for the clinician, due to its chemotherapeutic resistance. Recent findings suggest that targeting glioblastoma using anti-cancer natural polyphenols is a promising strategy. In this context, curcumin and berberine have been shown to have potent anti-cancer and anti-inflammatory effects against several malignancies. Due to the poor solubility and limited bioavailability, these compounds have limited efficacy for treating cancer. However, use of a formulation of curcumin with higher bioavailability or combining it with berberine as a co-treatment may be proving to be more efficacious against cancer. Recently, we demonstrated that solid lipid curcumin particles (SLCPs) provided more bioavailability and anti-cancer effects in cultured glioblastoma cells than did natural curcumin. Interestingly, a combination of curcumin and berberine has proven to be more effective in inhibiting growth and proliferation of cancer in the liver, breast, lung, bone and blood. However, the effect of combining these drugs for treating glioblastoma, especially with respect to its effect on activating the PI3K/Akt/mTOR pathways has not been studied. Therefore, we decided to assess the co-treatment effects of these drugs on two different glioblastoma cell lines (U-87MG and U-251MG) and neuroblastoma cell lines (SH-SY5Y) derived from human tissue. In this study, we compared single and combination (1:5) treatment of SLCP (20μM) and berberine (100 μM) on measures of cell viability, cell death markers, levels of c-Myc and p53, along with biomarkers of the PI3K/Akt/mTOR pathways after 24-48 h of incubation. We found that co-treatment of SLCP and berberine produced more glioblastoma cell death, more DNA fragmentation, and significantly decreased ATP levels and reduced mitochondrial membrane potential than did single treatments in both glioblastoma cells lines. In addition, we observed that co-treatment inhibited the PI3K/Akt/mTOR pathway more efficiently than their single treatments. Our study suggests that combination treatments of SLCP and berberine may be a promising strategy to reduce or prevent glioblastoma growth in comparison to individual treatments using either compound.

read more

PMID: 

Biomed Pharmacother. 2019 Jul ;115:108900. Epub 2019 May 1. PMID: 31054510

Abstract Title: 

Antidepressant-like effects of ginseng fruit saponin in myocardial infarction mice.

Abstract: 

BACKGROUND: Recently, the development of cardiovascular disease (CVD) has been proved to be closely associated with depression in which 5-HT plays a crucial role. Ginseng Fruit Saponin (GFS) and Metoprolol are two drugs which have beneficial effects on the cardiovascular system in Myocardial Infarction (MI) mice. However, their effects on depression-like behaviors after MI and its underlying mechanisms remain unknown. We aimed to investigate their antidepressive-like effects as well as their impacts on the 5-HT system.METHODS: The MI model was established by ligating left anterior descending coronary artery. Mice were administered with GFS, Metoprolol or saline for 4 weeks. Cardiac function was evaluated and depressive-like behaviors were quantified at the end of the experiments. Masson's staining was used to assess myocardial fibrosis while immunohistochemistry, western blot, ELISA and qPCR were performed to analyze the levels of 5-HT and its related genes.RESULTS: Compared with MI groups, Both GFS and Metoprolol treatments significantly improved cardiac function and reduced myocardial fibrosis. Moreover, GFS but not Metoprolol increased the levels of 5-HT in the cortex and rescued depression-like behaviors in MI mice.CONCLUSIONS: GFS has potential antidepressive effects and the mechanisms involve the regulation of 5-HT concentrations in the cortex.

read more

The U.S. Food and Drug Administration (FDA) recently announced a new guidance that could lead to the end of homeopathy in America in less than three months

PMID: 

J Ginseng Res. 2019 Oct ;43(4):606-617. Epub 2018 Aug 10. PMID: 31695567

Abstract Title: 

Hepatoprotective effect of ultrasonicated ginseng berry extract on a rat mild bile duct ligation model.

Abstract: 

Background: Theberry extract (GBE) is well known to have an antidiabetic effect. The aim of this study is to evaluate and investigate the protective effect of ultrasonication-processedberry extract (UGBE) compared with GBE on liver fibrosis induced by mild bile duct ligation (MBDL) model in rats. After ultrasonication process, the composition ratio of ginsenoside in GBE was changed. The component ratio of ginsenosides Rh1, Rh4, Rg2, Rg3, Rk1, Rk3, and F4 in the extract was elevated.Methods: In this study, the protective effect of the newly developed UGBE was evaluated on hepatotoxicity and neuronal damage in MBDL model. Silymarin (150 mg/kg) was used for positive control. UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg), GBE (250 mg/kg), and silymarin (150 mg/kg) were orally administered for 6 weeks after MBDL surgery.Results: The MBDL surgery induced severe hepatotoxicity that leads to liver inflammation in rats. Also, the serum ammonia level was increased by MBDL surgery. However, the liver dysfunction of MBDL surgery-operated rats was attenuated by UGBE treatment via myeloid differentiation factor 88-dependent Toll-like receptor 4 signaling pathways.Conclusion: UGBE has a protective effect on liver fibrosis induced by MBDL in rats through inhibition of the TLR4 signaling pathway in liver.

read more

PMID: 

Exp Ther Med. 2019 Dec ;18(6):4388-4396. Epub 2019 Oct 8. PMID: 31772634

Abstract Title: 

Ginseng berry aqueous extract prevents scopolamine-induced memory impairment in mice.

Abstract: 

Ginseng berry exhibits a diverse range of pharmacological activities. The present study aimed to examine the neuroprotective effects of ginseng berry aqueous extract (GBE) against oxidative stress and to assess the impact of GBE on memory impairment in mice. In HT-22 cells, GBE pretreatment significantly inhibited glutamate- and hydrogen peroxide-mediated cytotoxicity in a concentration-dependent manner, while treatment with up to 100µg/ml GBE alone did not change cell viability. In a murine model of scopolamine (SCP)-induced memory impairment, results from the passive avoidance test and the Morris water maze test indicated that GBE administration for 4 weeks prolonged step-through latency time and shortened escape latency time, suggesting that GBE can attenuate deficits in long-term memory induced by SCP. Additionally, GBE prevented SCP-induced reductions in acetylcholine by decreasing acetylcholinesterase activity and upregulating choline acetyltransferase mRNA levels in the hippocampus. GBE mitigated SCP-mediated mRNAdecreases in brain-derived neurotrophic factor levels and its associated signaling molecules. Furthermore, GBE administration significantly suppressed malondialdehyde production and increased glutathione levels, catalase activity and superoxide dismutase activity in SCP-induced memory impaired mice.Therefore, the results of the current study indicated that ginseng berry may be a potential candidate for treating or preventing memory deficits that are associated with neurodegenerative disorders.

read more

PMID: 

Molecules. 2019 Dec 9 ;24(24). Epub 2019 Dec 9. PMID: 31835292

Abstract Title: 

Review of Ginseng Anti-Diabetic Studies.

Abstract: 

Ginseng is one of the most valuable and commonly used Chinese medicines not only in ancient China but also worldwide. Ginsenosides, also known as saponins or triterpenoids, are thought to be responsible for the beneficial effects of ginseng. In this review, we summarize recent publications on anti-diabetic studies of ginseng extracts and ginsenosides in cells, animals, and humans. It seems that the anti-diabetic effect of ginseng is positive for type 2 diabetic patients but has no significant impact on prediabetes or healthy adults. Regulation of insulin secretion, glucose uptake, anti-oxidative stress, and anti-inflammatory pathways may be the mechanisms involved with ginseng's anti-diabetic effects. Taken together, this summary provides evidence for the anti-diabetes effects of ginseng extracts and ginsenosides as well as the underlying mechanisms of their impact on diabetes.

read more

PMID: 

BMC Res Notes. 2019 Dec 12 ;12(1):805. Epub 2019 Dec 12. PMID: 31831054

Abstract Title: 

Lycopene improves on basic hematological and immunological parameters in diabetes mellitus.

Abstract: 

OBJECTIVE: Diabetes is associated with an upset of hematological and immunological parameters in humans, however information on the effects of Lycopene is scarce. The aim of the study was to gain information on basic changes in hematological parameters as markers for safety since anemia as a complication in diabetic chemotherapy has been reported.RESULTS: Lycopene had anti-anemic effects and improved on the immune status of diabetic rats and these observations were dose independent. There was a decrease in neutrophil, low neutrophil-lymphocyte ratio and platelet counts and stable albumin, globulin levels. Lycopene could exert its protective effects through a balance of basic hematological physiological variables.

read more

PMID: 

Neurochem Res. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31728856

Abstract Title: 

Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat.

Abstract: 

The present study evaluated biochemical endpoints characterizing acrylamide (ACR) neurotoxicity in the cortex of rats, following the possible neuroprotective activity of thymoquinone (TQ), an active constituent of Nigella sativa. ACR (50 mg/kg, intraperitoneal [i.p.]) concurrently with TQ (2.5, 5 and 10 mg/kg, i.p.) for 11 days were administered to rats. As positive control, vitamin E was used. After 11 days of injections, narrow beam test (NBT) was performed. The levels of reduced glutathione (GSH) and malondialdehyde (MDA) were measured and Western blotting was done for mitogen-activated protein kinases (MAPKinases) and apoptosis pathways proteins in the rats' cortex. Additionally, Evans blue assay was done to evaluate the integrity of blood brain barrier (BBB). Administration of ACR significantly induced gait abnormalities. A significant decrease and increase in the levels of GSH and MDA was observed in the cortex of ACR-treated rats, respectively. The elevation in the levels of caspases 3 and 9, glial fibrillary acidic protein (GFAP) content, and Bax/Bcl-2, P-P38/P38 and P-JNK/JNK ratios accompanied by reductionin myelin basic protein (MBP) content and P-ERK/ERK ratio were noticed in the ACR group. TQ (5 mg/kg) improved gait abnormalities, and restored these changes. ACR affected the integrity of BBB while TQ was able to maintain the integrity of this barrier. TQ reversed the alterations in the protein contents of MAP kinase and apoptosis signaling pathways as well as MBP and GFAP contents, induced by ACR. It protected against ACR-mediated neurotoxicity, partly through its antioxidant and antiapoptotic properties.

read more