Rhein

$35.20
RV29

Rhein protect vital organs and improve glucose and lipid metabolism. Rhein to exhibit hepatoprotective, nephroprotective, anti-inflammatory, antioxidant, anti-cancer, and antimicrobial activities, as well as reducing chronic pancreatitis.

 

Ingredients

Rhubarb root
Rhein
Glycyrrhiza glabra

Other Ingredients: Vegetable cellulose (hypromellose); Vegetable Stearic Acid; Microcrystalline Cellulose and Vegetable Magnesium Stearate.

Does not contain: Wheat, gluten, soy, milk, eggs, fish, crustacean shellfish, tree nuts, peanuts

Rhein - The Anti-Bad

60 x 500 mg capsules

Actions

Anti-fibrotic effects:

Renal fibrosis

Hepatic fibrosis

Attenuates pancreatic fibrosis in chronic pancreatitis

Supports healthy kidney and liver function

Anti-inflammatory effects:

Lowers inflammation in chronic pancreatitis

Protects cartilage from osteoarthritic inflammation

Hepato-protective effects:

Improves lipid and cholesterol metabolism

Improve glucose metabolism and lower glucose blood levels

Increases insulin secretion

Anti-carcinogenic effects:

HER-2 & hormone-dependent breast cancer,

Gastric cancer

Colorectal cancer

Anti-oxidant

Indications

Hepatic fibrosis

Renal Fibrosis

Pre-diabetes

Diabetes

Diabetic nephropathy

Can be used as part of cancer protocols. Refer to Panaxea oncology resources for more information.

HER-2 & hormone-dependent breast cancer

Gastric cancer

Colorectal cancer

Staphylococcus aureus infection

Osteoarthritis

Chronic pancreatitis

Suggested Use:

2 caps daily

Caution:

may cause loose stools. Adjust dose 

Diabetes

Rhein has been used in traditional Chinese medicine with putative antidiabetic effects. Here we show that oral administration of Rhein for 6 weeks can significantly reduce fasting blood glucose (FBG) level, elevate the active glucagon-like peptide 1 (GLP-1) level, and increase the number of L-cells in the terminal ileum.

Wang et al., (2018) demonstrate that results indicate the modulation of the gut microbiota may play an essential role in the antidiabetic effects of Rhein.

Enteroendocrine cells (L Cells) are specialised cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect.

These findings by Wang raise the possibility that gut microbiota play an essential role in the antidiabetic effects of Rhein. In this study, we focus on how Rhein regulates gut microbiota and how it contributes to the enteroendocrine function.

Taken together, their study shows that oral administration of Rhein can significantly reduce the level of FBG and elevate GLP-1.

Gut Microbiota Play an Essential Role in the Antidiabetic Effects of Rhein.

Wang R, Zang P, Chen J, et al. Evidence-Based Complementary and Alternative Medicine Volume 2018, Article ID 6093282, https://doi.org/10.1155/2018/6093282

Different pharmacological experiments in a number of in vitro and in vivo models have convincingly demonstrated the abilities of Rhein to exhibit hepatoprotective, nephroprotective, anti-inflammatory, antioxidant, anti-cancer, and antimicrobial activities, as well as reducing chronic pancreatitis.

Summary of the in vitro and in vivo evidence for the biological activities of Rhein.

Pharmacological effect

In vitro evidence

In vivo evidence

Hepatoprotective activity

 

It modulates cytochrome P450 enzymes, protects hepatocyte from injury and prevents the progress of hepatic fibrosis in rats, alleviates glucose and lipid metabolism, increases energy expenditure, and restrains proinflammatory cytokine expression in mice.

Nephroprotective activity

It abolishes the a-smooth muscle actin (a-SMA) and fibronectin expression of NRK-49F cells.

It alleviates renal fibrosis in mice.It reduces intestinal permeability and protects the intestinal mucosa in immune globulin A nephropathy (18AN), halts the progression of lgAN, prevents the development of glomerulosclerosis, improves renal function, reduces renal fibrosis and Interstitial inflammation. and inhibits

the hypertrophy of renal proximal tubular epithelial cells in rats.

Chondroprotective activity

It inhibits cytokines LPS, TNF-a, and rhIL-ta)-induced effects in human osteoarthritic (OA) chondrocytes, human chondrosarcoma cell line HEM-055, human OA cartilage and synovial tissue cultures, human umbilical vein endothelial cells (HUVECs), and bovine and rabbit articular chondrocytes. In particular, it stimulates aggrecan production, promotes matrix formation, decreases the production of certain proinflammatory mediators (IL-1/3, IL-6, IL-8, and prostaglandin E2), corrects the matrix metalloproteinases/metalloproteinases imbalance, decreases IL-1 converting enzyme protein production, Inhibits proliferation of synoviocytes and chondrocytes, and suppresses cathepsin B activity and proteoglycan release.

 

Anti-Inflammatory activity

It reduces the transcription and expression of endothelial cell adhesion molecules.

It inhibits nicotinamide adenine dlnudeotide phosphate oxidase (p22phox gp9lphox) and cytokines (matrix metalloproteinase-2, activating transcript factor 6, and p66Shc).

Antioxidant activity

Antioxidant properties in human peripheral neutrophils, HUVECs, and beef heart submitochondrial particles.

It prevents the drug-induced oxidative damage in rats.

Anticancer activity

Anticarcinogenic effects In mouse epidermal cell 1136 line, human colon adenocarcinoma cells (Cato-2), human nasopharyngeal carcinoma (NPC) cells, HUVECs, and tongue cancer SCC-4 cells induce apoptosis in human hepatocellular carcinoma BEL-7902 cells. human cervical cancer Ca Ski cells, human promyelocytic leukemia cells (HL-60), human NPC cells, human tongue cancer cell line (SCC-9), human hepatoblastomaG2 (HepG2) cells, KB cells, and A-549 human lung cancer cells.

 

Antidiabetic activity

It inhibits transforming growth factor /3, and/or glucose transporter 1 overexpression in human and rat mesangial cells, inhibits glucose uptake in Ehrlich ascites tumor cells and human glomerular mesangial cells, and enhances glucose tolerance in 3T3-Li adipocytes.

It decreases glucose concentrations, increases insulin secretion, and/or improves glucose tolerance in db/db mice.

Antimicrobial activity

Antimicrobial effects against bacterium Helicobacter pylori and staphylococcus aureus (S. aureus)

 

Purgative activity

It induces ion secretion in human CaCo.2 monolayer cells and stimulates electrogenic chloride secretion in guinea pig colon.

It increases Na* and H2O flow in rat colon in-situ.

Lipid-lowering activity

It regulates cholesterol homeostasis and lipid and energy metabolism in 3T3-L1 and HepG2 cells.

It protects against obesity in mice.

Breast Cancer

Human breast cancers cells overexpressing HER2/neu are more aggressive tumours with poor prognosis, and resistance to chemotherapy. A study by Gang et aL., (2012) investigates anti-proliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2) and control vector MCF-7 (MCF-7/VEC) cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells (2). 

Rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. Li et al., (2012) conclude that rhein inhibits gastric inhibits cancer cell line (SGC-7901) proliferation by inducing apoptosis and this antitumuor effect of rhein is mediated in part by an intrinsic mitochondrial pathway (3).

Results showed that rhein remarkably inhibited breast cancer SK-Br-3 cell proliferation. The protein expressions of HER-2, NF-KB, and the protein phosphorylation of HER-2 were downregulated, however the protein expression of p53 and p21 was upregulated after rhein treatment. The level of HER-2 mRNA decreased by using RT-PCR assay and the level of HER-2 expression was also decreased by using immunofluorescence cytochemical assay after rheit treatment. It can be concluded that rhein could inhibit SK-Br-3 cell proliferation and induce apoptosis. HER-2/NF-kappaB/p53/p21 signal pathway might be involved in this process (4). 

Hypoxia is a hallmark of solid tumours, including breast cancer, and the extent of tumour hypoxia is associated with treatment resistance and poor prognosis. Considering the limited treatment of hypoxic tumour cells and hence a poor prognosis of breast cancer, the investigation of natural products as potential chemopreventive anti-angiogenic agents is of paramount interest. Rhein inhibits angiogenesis and the viability of hormone-dependent (MCF-7) or -independent (MDA-MB-435s) breast cancer cells in vitro under normoxic or hypoxic conditions.

Rhein inhibited the expression of hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF165), epidermal growth factor (EGF), and the phosphorylation of inhibitor of NF-κB (I-κB) under normoxic or hypoxic conditions. Taken together, these data indicate that rhein is a promising anti-angiogenic compound for breast cancer cell viability and growth (5).         

Rhein The Anti-Bad  blocks the uptake of glucose in tumour cells, causing changes in membrane associated functions to trigger cell death (6).

Rhein, a major compound in rhubarb, has been found to have anti-tumor properties in many human cancer cells. Ge et al., (2011) explored the potential of rhein as a chemotherapeutic agent on HCT- 116 cells and demonstrated significant inhibition of HCT-116 cells proliferation in both concentration (0, 10, 30, and 100 µM) and time (24, 48, and 72 h) dependent manners. The anti-tumor effects were associated with the introduction of cellular apoptosis, which was relative with reduction of Bcl-2, NF-κB and activation of caspase-9 and 3. These findings suggested that rhein inhibited the growth of HCT-116 through the intrinsic apoptotic pathway and might be a useful strategy of chemo- therapeutics of colon cancers.

Rhein had exerted cytotoxicity on human colon carcinoma HCT-116 cells, mainly through Bcl-2/BAX and NF-κB mediated caspase-activated apoptotic pathway and rhein has the potential to be developed as a chemotherapeutic or adjuvant agent on human colon cancers (7).

Antibacterial 

Rhein has been reevaluated as an antibacterial agent against Staphylococcus aureus in 2008 (8). Synergy or partial synergy has been demonstrated between rhein and the antibiotics oxacillin and ampicillin (9).

Diabetic nephropathy

Diabetic nephropathy (DN) is characterized by unclear pathogenesis. Recent medical data shows that the incidence of DN rises year by year. Rhein is the main compositions of rhubarb, a traditional Chinese medicinal plant, which plays an active role in kidney protection. The prophylaxis and phytotherapeutic effects of rhein are due to its anti-inflammatory and antifibrosis properties. Zeng et al., shed light on the renal protective role of rhein in diabetes mellitus (DM) with a particular focus on the molecular basis of this effect (10).

References

1. Yan-Xi Zhou, Wei Xia, Wei Yue, Cheng Peng, Khalid Rahman, and Hong Zhang, “Rhein: A Review of Pharmacological Activities,” Evidence-Based Complementary and Alternative Medicine, vol. 2015, Article ID 578107, 10 pages, 2015. doi:10.1155/2015/578107

2. Chang CY, Chan HL, Lin HY, et al. Rhein induces apoptosis in human breast cancer cells. Evid Based Complement Alternat Med. 2012;2012:952504. doi: 10.1155/2012/952504.

3. Yiwen Li, Yuqing Xu, Bo Lei,et al.  Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway. Braz J Med Biol Res. 2012 Oct; 45(11): 1052–1059. doi:  10.1590/S0100-879X2012007500125

4. Lin YJ , Huang YH , Zhen YZ , Liu XJ , Zhen YS. Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway.  Yao xue xue bao = Acta Pharmaceutica Sinica [2008, 43(11):1099-1105] 

5. Fernand VE, Losso JN, Truax RE, et al. Rhein inhibits angiogenesis and the viability of hormone-dependent and -independent cancer cells under normoxic or hypoxic conditions in vitro. Chemico-Biological Interactions. Volume 192, Issue 3, 15 July 2011, Pages 220–232

6. Aihua Zhang, Hui Sun, Bo Yang and Xijun Wang Predicting new molecular targets for rhein using network pharmacology DOI: 10.1186/1752-0509-6-20

7. Ge X, Luo Xf, Chen Yg, et al. Rhein induces apoptosis of HCT-116 human colon cancer cells via activation of the intrinsic apoptotic pathway. African Journal of Biotechnology Vol. 10(61), pp. 13244-13251, 10 October, 2011

8.Yu L, Xiang H, Fan J, et al. (2008). Global transcriptional response of Staphylococcus aureus to rhein, a natural plant product. J Biotechnol. 135 (3): 304–308. doi:10.1016/j.jbiotec.2008.04.010. PMID 18514345.

9. Joung DK, Joung H, Yang DW, et al. (2012). Synergistic effect of rhein in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. Exp Ther Med. 3 (4): 608–612. doi:10.3892/etm.2012.459. PMC 3438619Freely accessible. PMID 22969937.

10. Zeng C-C, Liu X, Chen G-R et al. The Molecular Mechanism of Rhein in Diabetic Nephropathy. Evidence-Based Complementary and Alternative Medicine. Volume 2014 (2014) http://dx.doi.org/10.1155/2014/487097