Ethnopharmacology of Rubus idaeus Linnaeus: A critical review on ethnobotany, processing methods, phytochemicals, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus idaeus Linnaeus (RI) is a Chinese herbal medicine that has been widely used in China for a long time to reinforce the kidney, nourish the liver, improve vision, and arrest polyuria. AIM OF THE STUDY: This work aims to evaluate the recent progress of the chemical composition, pharmacological activity, pharmacokinetics, metabolism, and quality control and of Rubus idaeus, which focuses on the insufficiency of existing research and will shed light on future studies of Rubus idaeus. METHODS: Literatures about "Rubus idaeus","Red raspberry" and "Fupenzi"are retrieved by browsing the database, such as Web of Science (http://www.webofknowledge.com/wos), Pubmed (https://pubmed.ncbi.nlm.nih.gov/), CNKI (http://www.cnki.net/), and Wanfang Data (http://www.wanfangdata.com.cn). In addition, related textbooks and digital documents are interrogated to provide a holistic and critical review of the topic. The period of the literature covered from 1981 to 2022. RESULTS: Approximately 194 compounds have been isolated from Rubus idaeus, which is rich in phenols, terpenoids, alkaloids, steroids, and fatty acids. Numerous investigations have demonstrated that Rubus idaeus exhibits many pharmacological activities, including hypoglycemic and hypolipidemic, anti-Alzheimer effect, anti-osteoporosis, hepatoprotective, anti-cancer, neuroprotective, anti-bacteria and skin care, etc. However, it is worth noting that most of the research is not associated with the conventional effect, such as reducing urination and treating opacity of the cornea. CONCLUSION: The effectiveness of Rubus idaeus has been proved by its long-term clinical application. The research on the pharmacological activity of Rubus idaeus has flourished. In many pharmacological experiments, only the high-dose group can achieve the corresponding efficacy, so the efficacy of Rubus idaeus needs to be further interrogated. Meanwhile, the relationship between pharmacological activity and specific compounds of Rubus idaeus has not been clarified yet. Last but not least, studies involving toxicology and pharmacokinetics are very limited. Knowledge of bioavailability and toxicological behavior of Rubus idaeus can help understand the herb's pharmacodynamic and safety profile.

Phlorizin alleviates cholinergic memory impairment and regulates gut microbiota in d-galactose induced mice.

We explored the effect of phlorizin against cholinergic memory impairment and dysbacteriosis in D-galactose induced ICR mice. The control (CON) group, D-galactose model (DGM) group, and three groups (DG-PL, DG-PM, DG-PH) treated with phlorizin at 0.01%, 0.02%, and 0.04% (w/w) in diets were raised for 12 weeks. Supplementing with phlorizin reversed the loss of organ coefficient and body weight caused by D-galactose. The functional abilities of phlorizin on hippocampal-dependent spatial learning and memory, anti-oxidation, anti-inflammation were also observed. Meanwhile, phlorizin intervention upregulated the gene expression of Nrf2, GSH-PX, SOD1, decreased the gene expression of NF-κB, TLR-4, TNF-α, and IL-1ß in the hippocampus, while enhanced the gene expression of JAM-A, Mucin2, Occludin in the caecum. Furthermore, a neurotransmitter of acetylcholine (ACh) was enhanced, while acetylcholinesterase (AChE) activity was inhibited by phlorizin administration. Moreover, phlorizin administration increased short-chain fatty acids (SCFAs) content, and reduced lipopolysaccharides (LPS) levels, which may relate to the rebuilding of gut microbiota homeostasis. Treatment with phlorizin may be an effective intervention for alleviating cognitive decline and gut microbiota dysbiosis.

Iridoids and polyphenols from chilean Gaultheria spp. berries decrease the glucose uptake in Caco-2 cells after simulated gastrointestinal digestion.

Berries are rich food sources of potentially health-beneficial (poly)phenols. However, they may undergo chemical modifications during gastrointestinal digestion. The effect of simulated gastrointestinal digestion on the content and composition of secondary metabolites from Gaultheria phillyreifolia and G. poeppigii berries was studied. The influence of the digested extracts on the in vitro metabolism and absorption of carbohydrates was evaluated. After simulated digestion, 31 compounds were detected by UHPLC-DAD-MS. The total content of anthocyanins decreased by 98-100%, flavonols by 44-56%, phenylpropanoids by 49-75% and iridoids by 33-45%, the latter showing the highest stability during digestion. Digested extracts inhibited α-glucosidase (IC50 2.8-24.9 µg/mL) and decreased the glucose uptake in Caco-2 cells by 17-28%. Moreover, a decrease in the mRNA expression of glucose transporters SGLT1 (38-92%), GLUT2 (45-96%), GLUT5 (28-89%) and the enzyme sucrase-isomaltase (82-97%) was observed. These results show the effect of simulated gastrointestinal digestion on the content and composition of Gaultheria berries.

Phlorizin from sweet tea inhibits the progress of esophageal cancer by antagonizing the JAK2/STAT3 signaling pathway.

Phlorizin, an important member of the dihydrochalcone family, has been widely used as a Chinese Traditional Medicine for treatment of numerous diseases. The present study aimed to investigate the potential therapeutic effects of phlorizin on esophageal cancer. Phlorizin, extracted from sweet tea, was used to treat esophageal cancer cells. Cell proliferation, migration and invasion were determined using Cell Counting Kit­8 and colony formation assays, and wound healing and Transwell assays, respectively. RNA sequencing and bioinformatics analysis was used to investigate the potential mechanism of phlorizin in the development of esophageal cancer. Fluorescent staining and flow cytometry was used to measure the level of apoptosis. The expression level of the proteins, P62/SQSTM1 and LC3 Ð†/II, and the effect of phlorizin on the JAK2/STAT3 signaling pathway was detected using western blot analysis. The results demonstrated that phlorizin could inhibit cell proliferation, migration and invasion. Bioinformatics analysis showed that phlorizin might be involved in pleiotropic effects, such as the 'JAK/STAT signaling pathway' (hsa04630), 'MAPK signaling pathway'(hsa04010) and 'apoptosis' (hsa04210). It was also confirmed that phlorizin promoted apoptosis and inhibited autophagy in the esophageal cancer cells. Notably, phlorizin might inhibit the proteins in the JAK/STAT signaling pathway, which would affect cancer cells. Taken together, the present data showed that phlorizin inhibited the progression of esophageal cancer by antagonizing the JAK2/STAT3 signaling pathway.

Dietary Supplementation of Apple Phlorizin Attenuates the Redox State Related to Gut Microbiota Homeostasis in C57BL/6J Mice Fed with a High-Fat Diet.

We explored the effects of dietary supplementation with phlorizin on redox state-related gut microbiota homeostasis in an obesity mouse model. Mice (C57BL/6J) were grouped as follows for 12 weeks: normal chow diet group (NCD), high-fat and cholesterol diet group (HFD), and treatment groups fed with HFD along with three levels of phlorizin. Phlorizin alleviated the hyperlipidemia and redox status and increased the total ccal SCFA content (1.88 ± 0.25 mg/g). Additionally, phlorizin regulated gene expression related to lipid metabolism, redox status, and cecum barrier and rebuilt gut microbiota homeostasis. After interference by antibiotics, the total phloretin content in the feces was decreased about 4-fold, and most of the health-promoting effects were abolished, indicating that phlorizin might be susceptible to microbial biotransformation and that microecology is indispensable for maintaining the redox state capacities of phlorizin. Phlorizin treatment could be an advantageous option for improving HFD-related obesity and redox states related to gut microbiota homeostasis.

Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity.

Phlorizin (PHZ) is one of phytonutrients in apples that contributes to the health-promoting effect implicated by the saying, 'an apple a day keeps the doctor away'. PHZ was firstly identified as a competitive inhibitor of sodium-glucose co-transporters-2 (SGLT2); however, its low bioavailability makes it hard to fully explain its pharmacological mechanisms. This study aimed to investigate the ameliorating effect of PHZ on high-fat diet (HFD)-induced obesity via modulating the "gut microbiota-barrier axis". Firstly, C57BL/6 J mice were fed a normal chow diet (NCD) or HFD coadministered with or without PHZ for 12 weeks. Our results showed that PHZ supplementation significantly reduced HFD-induced body weight gain (P < .001), alleviated metabolic disorders (MDs) like insulin resistance (P < .001) and elevation of serum lipopolysaccharides (LPS) (P < .001), attenuated HFD-induced gut microbiota alterations, enhanced short-chain fatty acids (SCFAs) production (P < .001), and inhibited fecal LPS production (P < .001). To investigate the role of the fecal microbiota in the observed beneficial effects, a fecal microbiota transplantation (FMT) experiment was performed by transplanting the feces of the four groups of mice (as donor mice) daily collected from the fourth week to a new batch of acclimatized HFD-fed mice. Our results confirmed that feeding the gut contents of the PHZ-modulated mice could attenuate HFD-induced MDs, accompanied by enhanced glucagon-like peptide 2 (GLP-2) secretion (P < .001) and restoration of HFD-induced damage in the gut epithelial barrier. This study has provided evidence that the "gut microbiota-barrier axis" was an alternative target for the anti-obesity effect of PHZ. This work has also provided an explanation for the high efficacy of PHZ despite the low bioavailability, and PHZ holds great potential to be developed as a functional food ingredient.

Evaluation of Apple Pomace Flour Obtained Industrially by Dehydration as a Source of Biomolecules with Antioxidant, Antidiabetic and Antiobesity Effects.

Apple pomace flour (APF) obtained at industrial scale level by the application of innovative technological process (dehydration (5 h, T ≤ 55 °C), grinding (300 µm)) was evaluated as a source of bioactive compounds with antioxidative, antiobesity and antidiabetic effects. Proximate composition, individual (HPLC-DAD-MS/MS) and total phenols (TPC) as well as flavonoids content (TFC), antioxidant (AO) activity (DPPH, ABTS, HPMC), water and oil holding capacity (WHC and OHC) of APFs obtained from apple pomace from mixed and individual apple cultivars grown conventionally and organically were compared. The effect of APF supplementation on the glycaemic status and glucose tolerance (oral glucose tolerance test (OGTT)) of C57BL/6J mice exposed to high-fat and sucrose diet was examined. High K content (4.2-6.4 g/kg), dietary fibres (35-45 g/100 g), TPC (4.6-8.1 mg GAE/g), TFC (18.6-34.6 mg QE/g), high water and oil holding capacity (4.7-6.4 and 1.3-1.6 g/g) were observed in the APFs. Content of major phenols (phlorizin, chlorogenic acid, quercetin), TPC and TFC correlated highly with prominent AO activity. APF supplementation lowered the increase of body weight gain and blood glucose, and improved glucose tolerance significantly. Health-promoting biomolecules, AO activity, functional properties and prevention of diet-driven glucose metabolism disorders pave the way to APF exploitation in human nutrition.

Biocatalytic Production of a Potent Inhibitor of Adipocyte Differentiation from Phloretin Using Engineered CYP102A1.

In this study, we investigated an efficient enzymatic strategy for producing potentially valuable phloretin metabolites from phlorizin, a glucoside of phloretin that is rich in apple pomace. Almond ß-glucosidase efficiently removed phlorizin's glucose moiety to produce phloretin. CYP102A1 engineered by site-directed mutagenesis, domain swapping, and random mutagenesis catalyzed the highly regioselective C-hydroxylation of phloretin into 3-OH phloretin with high conversion yields. Under the optimal hydroxylation conditions of 15 g cells L-1 and a 20 mM substrate for whole-cell biocatalysis, phloretin was regioselectively hydroxylated into 3.1 mM 3-OH phloretin each hour. Furthermore, differentiation of 3T3-L1 preadipocytes into adipocytes and lipid accumulation were dramatically inhibited by 3-OH phloretin but promoted by phloretin. Consistent with these inhibitory effects, the expression of adipogenic regulator genes was downregulated by 3-OH phloretin. We propose a platform for the sustainable production and value creation of phloretin metabolites from apple pomace capable of inhibiting adipogenesis.

UHPLC-ESI-HRMS/MS analysis on phenolic compositions of different E Se tea extracts and their antioxidant and cytoprotective activities.

E Se tea, prepared from the leaves of Malus toringoides (Rehd.) Hughes, is a traditional beverage, but there is little known about its chemical substances. This paper is aimed to investigate the chemical composition, antioxidant, and cytoprotective activities of the extract and fractions from E Se tea. Sixteen compounds were characterized by UHPLC-ESI-HRMS/MS. Phloridzin was the main compound, especially in ethyl acetate fraction (EAF). Moreover, EAF had the highest total phenolic and flavonoid contents with 197.54 ± 7.52 mg gallic acid equivalents/g extract and 85.94 ± 5.39 mg rutin equivalents/g extract, respectively, and exhibited the strongest antioxidant capacity (DPPH: IC50 = 54.91 ± 3.38 µg/mL; ABTS: IC50 = 98.08 ± 6.92 µg/mL). Different fractions of E Se tea, especially EAF, significantly inhibited intracellular ROS generation, reduced cell apoptosis, and decreased oxidative stress damage in H2O2-induced HepG-2 cells. Therefore, the obtained results highlight that E Se tea is a promising source for functional beverage or nutritional foods.

Simultaneous extraction and separation of bioactive compounds from apple pomace using pressurized liquids coupled on-line with solid-phase extraction.

The objective of this work was the development of an on-line extraction/fractionation method based on the coupling of pressurized liquid extraction and solid-phase extraction for the separation of phenolic compounds from apple pomace. Several variables of the process were evaluated, including the amount of water of the first stage (0-120 mL), temperature (60-80 °C), solid-phase extraction adsorbent (Sepra, Isolute, Strata X and Oasis) and activation/elution solvent (methanol and ethanol). The best results were observed with the adsorbent Sepra. The temperature had a small effect on recovery, but significant differences were observed for phlorizin and a quercetin derivative. Results indicate that ethanol can be used to replace methanol as an activation, extraction/elution solvent. While using mostly green solvents (water, ethanol, and a small amount of methanol that could be reused), the developed method produced higher or similar yields of acids (2.85 ± 0.19 mg/g) and flavonoids (0.97 ± 0.11 mg/g) than conventional methods.

Risk of reduced intestinal absorption of myo-inositol caused by D-chiro-inositol or by glucose transporter inhibitors.

Background: D-chiro-inositol (DCI) and glucose transporter inhibitors may inhibit myo-inositol (MI) transporters, and the aim is to clinically evaluate their effect on MI absorption. Research design and methods: Fasting 18 healthy volunteers received orally 6000 mg MI, 6000 mg MI with 1000 mg DCI, and 6000 mg MI with SelectSIEVE® Apple PCQ and Sorbitol, Maltodextrin and Sucralose (PCQ-SMS), in three different phases with a washout period of 7 days. At each phase, blood samples were collected before administration, and every 60 minutes until 540 minutes after administration. MI plasma levels (µmol/L) were quantified by gas chromatography-mass spectrometry; maximum plasma concentration (Cmax), time to reach it (Tmax), and the area under the time-concentration curve of MI (AUC 0-540) were evaluated. Results: The Cmax of MI alone (Tmax = 180min) was 1.29-fold higher than those of MI with DCI (Tmax = 180min) (p < 0.001) and 1.69-fold higher than those of MI with PCQ-SMS (Tmax = 240min) (p < 0.001). The AUC 0-540 was reduced by 19.09% in MI plus DCI (p = 0.0118) and by 31.8% in MI plus PCQ-SMS (p < 0.001) as compared to MI alone. Conclusions: DCI, glucose transporter inhibitors and sugars, such as sorbitol and maltodextrin, seem to inhibit MI absorption, decreasing MI plasma concentration as compared to MI alone.

Apple phlorizin attenuates oxidative stress in Drosophila melanogaster.

Apple phlorizin has a lot of applications owing to its antioxidant and hepatoprotective properties. This study explored the antioxidant effects and life span-prolonging activity of apple phlorizin in Drosophila melanogaster. Treatment with apple phlorizin was found to significantly extend the life span and ameliorate the age-related decline of locomotor function. This life span-extending activity was associated with the increased activity of superoxide dismutase, catalase, mRNA expression of glutamate-cysteine ligase catalytic subunit, cap-n-collar (cnc, homologue of mammalian Nrf2 gene), Keap1, and deacetylase sir2, as well as the downregulation of methuselah. Computational analysis suggested phlorizin could work as a Nrf2 activator and exert its biological activities by interfering with the Keap1 and Nrf2 binding. Therefore, it was concluded that the antioxidant and anti-aging effects of phlorizin might, at least in part, be mediated through the cooperation with the endogenous stress defense system. PRACTICAL APPLICATIONS: Phlorizin, from apple peel, has been used as a nutrient for over 100 years. To date, despite extensive research on phlorizin, a report on its effect on the antioxidant system in fruit flies is yet lacking. This report demonstrates that phlorizin can exert a protective effect on antioxidant issues and prolong life in fruit flies, which is valuable in the rational utilization of phlorizin in functional foods.

Purified Phlorizin from DocynIa Indica (Wall.) Decne by HSCCC, Compared with Whole Extract, Phlorizin and Non-Phlorizin Fragment Ameliorate Obesity, Insulin Resistance, and Improves Intestinal Barrier Function in High-Fat-Diet-Fed Mice.

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.

Characterization of phenolic and other polar compounds in peel and flesh of pink guava (Psidium guajava L. cv. 'Criolla') by ultra-high performance liquid chromatography with diode array and mass spectrometric detection.

Pink guava (Psidium guajava L.) is a highly consumed fruit in tropical countries. Despite of interesting research on health effects of this fruit, investigations into the profile of secondary plant metabolites are scarce. In this study, the phenolic compounds in the peel and flesh of pink guava were characterized by ultra-high performance liquid chromatography with diode array and mass spectrometric detection. Sixty phenolic compounds were characterized by MS2 and classified as ellagitannins, flavones, flavonols, flavanols, proanthocyanidins, dihydrochalcones, and anthocyanidins, and non-flavonoids such as phenolic acid derivatives, stilbenes, acetophenones, and benzophenones. Forty-two polyphenols are reported for the first time in both peel and flesh, and twenty-four compounds were detected for the first time in P. guajava, e.g., phlorizin, nothofagin, astringin, chrysin-C-glucoside, valoneic acid bilactone, cinnamoyl-glucoside, and two dimethoxycinnamoyl-hexosides.

Dietary phlorizin enhances osteoblastogenic bone formation through enhancing ß-catenin activity via GSK-3ß inhibition in a model of senile osteoporosis.

Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss with advancing age has become a grave public health concern. This study examined whether phlorizin and phloretin, dihydrochalcones in apple peels, inhibited senile osteoporosis through enhancing osteoblastogenic bone formation in cell-based and aged mouse models. Submicromolar phloretin and phlorizin markedly stimulated osteoblast differentiation of MC3T3-E1 cells with increased transcription of Runx2 and osteocalcin. Senescence-accelerated resistant mouse strain prone-6 (SAMP6) mice were orally supplemented with 10 mg/kg phlorizin and phloretin daily for 12 weeks. Male senescence-accelerated resistant mouse strain R1 mice were employed as a nonosteoporotic age-matched control. Oral administration of ploretin and phorizin boosted bone mineralization in all the bones of femur, tibia and vertebra of SAMP6. In particular, phlorizin reduced serum RANKL/OPG ratio and diminished TRAP-positive osteoclasts in trabecular bones of SAMP6. Additionally, treating phlorizin to SAMP6 inhibited the osteoporotic resorption in distal femoral bones through up-regulating expression of BMP-2 and collagen-1 and decreasing production of matrix-degrading cathepsin K and MMP-9. Finally, phlorizin and phloretin antagonized GSK-3ß induction and ß-catenin phosphorylation in osteoblasts and aged mouse bones. Therefore, phlorizin and phloretin were potential therapeutic agents encumbering senile osteoporosis through promoting bone-forming osteoblastogenesis via modulation of GSK-3ß/ß-catenin-dependent signaling.

Antidiabetic Properties of an Apple/Kale Extract In Vitro, In Situ, and in Mice Fed a Western-Type Diet.

Type 2 diabetes mellitus (T2DM) is a common and increasingly prevalent metabolic disorder, and effective preventive strategies against this disease are needed. The aim of the present study was to evaluate the potential antidiabetic properties of a dietary apple/kale extract (AKE), which was rich in phlorizin and flavonoids, in laboratory mice. Mice were fed a control diet, a Western-type high-sugar, high-fat diet (WTD), or a WTD plus AKE for 10 weeks. Body weight, food and energy intake, body composition, and blood glucose level were recorded in addition to the postprandial rise in blood glucose concentration after a single administration of glucose (oral glucose tolerance test, OGTT). Furthermore, changes in glucose-induced short-circuit current (ISC) in response to AKE and phlorizin administration were evaluated in situ in intestinal tissues with Ussing chambers. In addition, the in vitro inhibition of α-glucosidase by AKE was determined. The present data suggest that supplementation of an AKE to a WTD significantly improved both blood glucose levels and OGTT in mice. Furthermore, in situ uptake of glucose was significantly inhibited by AKE. Finally, we showed that AKE significantly inhibits α-glucosidase activity in vitro. We conclude that AKE exhibits antidiabetic properties by a dual mechanism, including the inhibition of α-glucosidase and sodium-dependent glucose transporter 1 (SGLT1). Thus, AKE has the potential to serve as a natural plant bioactive compound for dietary prevention strategies against T2DM.

Simultaneous separation and purification of chlorogenic acid, epicatechin, hyperoside and phlorizin from thinned young Qinguan apples by successive use of polyethylene and polyamide resins.

The method for separating and purifying chlorogenic acid (CA), epicatechin (EC), hyperoside (HY) and phlorizin (PH) simutaneously from young Qinguan apples by successive use of X-5 and polyamide resins has been developed in this study. The order of adsorption capacities of X-5 for the four phenolics was PH>HY>EC>CA, and the adsorption equilibriums of the four phenolics onto X-5 resin conformed to Langmuir isotherms preferentially. The adsorption kinetics of EC and CA onto X-5 conformed to the pseudo-first-order model, while that of HY and PH accorded with the pseudo-second-order model. Interestingly, the values of equilibrium adsorption capacities (Qe) calculated in the preferential kinetics models were closer to that of theoretical maximum adsorption capacities (Q0) calculated by Langmuir isotherms. Through dynamic adsorption and desorption using X-5 and polyamide resins with ethanol solution as strippant, CA, EC, HY and PH were obtained with purities of 96.21%, 95.34%, 95.36% and 97.36%, respectively.

Research progress on traditional Chinese medicine against diabetes based on intestinal flora new targets / 药物评价研究

Diabetes has become the third largest killer to human life and health,and its development is closely related to the intestinal flora imbalance caused by series of consequences.So adjusting the structure of intestinal flora becomes a new idea for the treatment of diabetes.Traditional Chinese medicine (TCM) has good curative effect in prevention and treatment of diabetes,and improvement on the structure of intestinal flora may be one of its important mechanisms.The article reviewed the research progress on prevention and treatment of diabetes by TCM single components (berberine,phloridzin,rheinic acid,etc),TCM single prescription (essential oil from Cinnamomum cassia,flower stalk of Coptis chinensis,total coumarin of Feucedani Radix) and TCM priscriptions (Gegen Qinlian Decoction,Shengjiang Powder,Buzhong Yiqi Decoction,Huanglian Jiedu Decoction,Wenyang Yiqi Huoxue Compound,etc.) based on new targets in intestinal flora,so as to provide reference for the development of TCM for prevention and treatment of diabetes.

Research progress on traditional Chinese medicine against diabetes based on intestinal flora new targets / 药物评价研究

Diabetes has become the third largest killer to human life and health,and its development is closely related to the intestinal flora imbalance caused by series of consequences.So adjusting the structure of intestinal flora becomes a new idea for the treatment of diabetes.Traditional Chinese medicine (TCM) has good curative effect in prevention and treatment of diabetes,and improvement on the structure of intestinal flora may be one of its important mechanisms.The article reviewed the research progress on prevention and treatment of diabetes by TCM single components (berberine,phloridzin,rheinic acid,etc),TCM single prescription (essential oil from Cinnamomum cassia,flower stalk of Coptis chinensis,total coumarin of Feucedani Radix) and TCM priscriptions (Gegen Qinlian Decoction,Shengjiang Powder,Buzhong Yiqi Decoction,Huanglian Jiedu Decoction,Wenyang Yiqi Huoxue Compound,etc.) based on new targets in intestinal flora,so as to provide reference for the development of TCM for prevention and treatment of diabetes.

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents.

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.