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Background Puerarin is an isoflavone derivative isolated from the traditional Chinese medicine Pueraria Lobelia, which has proven to relieve depression-like behavior. However, its underlying antidepressant mechanisms have been poorly characterized. Herein, we explored whether Puerarin's antidepressant effect is associated with changes in the gut microbiota (GM). Methods The model of depression in mice featuring chronic unpredictable mild stress (CUMS) was eastablished, and its antidepressant effect was estimated by sugar water preference and forced swimming test. Genomic DNA extracted from fecal samples was employed to sequence the 16S rRNA gene for gut microbiota identification. Results Puerarin (100 mg/kg) treatment was found to alleviate the CUMS-induced depression-like behaviors. Furthermore, chronic stress led to pathological microbial flora, which was principally marked by the increased abundance of pathogenic bacteria (Proteobacteria, Flexispira, Desulfovibrio) and the decreased abundance of beneficial bacteria (Firmicutes, Bacillales, Lactobacillus). Intriguingly, puerarin treatment reversed these changes. Limitations The specific role and anti-depression mechanism of characteristic gut microflora were not confirmed. Conclusion Puerarin can remedy stress-induced disruptions of normal gut microflora. It is suggested that the antidepressant mechanism of puerarin may closely interact with restoring beneficial microflora.

Influenza is an acute viral respiratory disease that can also cause gastroenteritis-like symptoms, such as abdominal pain, nausea, vomiting, and diarrhea. Immune dysfunction of adipose tissue is involved in the occurrence and prognosis of influenza viral pneumonia. In this study, we analyzed intestinal and adipose immune responses in mice infected with influenza virus and found that the impairment of intestinal and adipose immunity to influenza virus infection could be reversed by treatment with puerarin, a medicinal compound isolated from Pueraria lobata (called “gegen” in Chinese). We found that the lungs, small intestines (duodenum, ileum, jejunum) and large intestines (colon and rectum) of infected mice showed obvious inflammatory lesions, with significantly increased levels of virus, inflammatory cytokines (interleukin [IL]-6, IL-17, and tumor necrosis factor-α), Toll-like receptors 3, 4, and 9, and integrin αvβ3 and α4, and a decreased level of secreted IgA compared to the normal control group (NC) (P < 0.05-0.001). Influenza virus infected mesenteric lymph nodes and adipose tissue, and adipokines (leptin, visfatin, “chemerin”, and adiponectin) of lung and mesenteric adipose tissue were dysregulated. Puerarin treatment reversed the impairment of the intestinal and adipose immune responses in mice infected with influenza virus. Our findings suggest that influenza virus can infect adipose tissue and lead to intestinal adipose immune dysfunction in normal-weight mice and that the impairment of the intestinal and adipose immune response to influenza virus infection can be reversed by puerarin treatment.

The indispensable role of Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in Amyloid beta (Aβ) plaques generation and Aβ-mediated synaptic dysfunctions makes it a crucial target for therapeutic intervention in Alzheimer's disease (AD). In order to find out the potential inhibitors of BACE1, the present study focused on five phytochemicals from Pueraria tuberosa, namely, daidzin, genistin, mangiferin, puerarin, and tuberosin. A molecular docking study showed that all five phytochemicals presented the strongest BACE1 inhibition. Integrated molecular dynamics simulations and free energy calculations demonstrated that all five natural compounds have stable and favorable energies causing strong binding with the pocket site of BACE1 on 50 ns. All these molecules also passed Lipinski's rule of five. To validate the molecular modeling based findings, we primarily targeted the cognitive decline associated with BACE1 expression in AD flies with P. tuberosa. Significant improvement in cognitive decline was observed in AD flies in different behavioral assays such as Larval crawling assay (16.38%), Larval light preference assay (26.39%), Climbing assay (32.97%), Cold sensitivity assay (43.6%), and Thermal sensitivity assay (44.42%). The present findings suggest that P. tuberosa may be considered as a promising dietary supplement that can significantly ameliorate cognitive decline caused by BACE1 in Alzheimer's disease (AD).

As a functional bowel disorder, irritable bowel syndrome (IBS), especially IBS-diarrhea (IBS-D), affects approximately 9-20% of the population worldwide. Classical treatments for IBS usually result in some side effects and intestinal microbial disorders, which inhibit the clinical effects. Natural edible medicines with beneficial effects and few side effects have received more attention in recent years. Puerarin is the main active ingredient in pueraria and has been used in China to treat splenasthenic diarrhea and as a natural food in folk medicine for hundreds of years. However, there have been no reports of using puerarin in the treatment of IBS-D, and the underlying mechanism is also still unclear. In this study, a comprehensive model that could reflect the symptoms of IBS-D was established by combining neonatal maternal separation (NMS) and adult colonic acetic acid stimulation (ACAAS) in rats. The results showed that puerarin could reverse the abdominal pain and diarrhea in IBS-D rats. The therapeutic effect was realized by regulating the richness of the gut microbiota to maintain the stabilization of the intestinal micro-ecology. Furthermore, the possible mechanism might be related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis by the suppressed expression of corticotropin-releasing hormone receptor (CRF) 1. At the same time, intestinal function was improved by enhancing the proliferation of colonic epithelial cells by upregulating the expression of p-ERK/ERK and by repairing the colonic mucus barrier by upregulating occludin expression. All these results suggest that puerarin could exert excellent therapeutic effects on IBS-D.

Pueraria lobata is utilized as a food source in China. The aim of this study is to combine virtual screening and molecular dynamics predictive model to screen out the potential synaptic plasticity-maintaining components from the root of P. lobate and to verify it by employing the amyloid β-injected rats' model. Eighteen compounds were identified by HPLC-MS/MS; puerarin manifested the most potential to form a stable complex with calcium/calmodulin kinase IIα (CaMK IIα), which is the key protein in synaptic plasticity by the in silico study. The further in vivo assay showed that puerarin could elevate the synaptic thickness, density, and length, relieve calcium overload, regulate the expression of CaMK IIα, and other p38MAPK-CREB signaling pathway-related biochemical criteria. The behavioral test also verified the results. Results have confirmed that the root of P. lobate can work anti-AD by maintaining the synaptic plasticity and proved the reliability of using the in silico predictive model to determine active ingredients from the natural product.

Puerarin is an isoflavone isolated from the medicinal plant Pueraria lobata. The purpose of this study was to study the antiinflammatory and antimatrix-degrading effects of puerarin in a rat osteoarthritis (OA) model and its protective effects on joints. The rat OA model was established by anterior cruciate ligament transection (ACLT) surgery. Rats (n = 40) were divided into nontreated OA, OA + celecoxib (2.86 mg/kg), OA + puerarin (50 and 100 mg/kg), and control groups. Two weeks after surgical induction, puerarin was administered by gavage daily for 8 weeks. After 8 weeks, macroscopic observation and histopathological images showed that cartilage damage was reduced after puerarin and celecoxib treatment, the intensity of Safranin O staining was high, and the OARSI scores were significantly reduced compared to the OA group. Puerarin reduced the expression of MMP-3, MMP-13, ADAMTS-5, and COX-2 in the cartilage tissue of ACLT rats, inhibited the production of IL-1β, IL-6, and TNF-α inflammatory factors, increased Type II collagen content, and altered the expression of serum OA cartilage degradation/bone turnover biomarkers (CTX-I, CTX-II, COMP, and PIINP). Based on these findings, we speculate that puerarin supplement to attain recovery from OA damage.

Puerarin (PU) is the most abundant isoflavone from the root of Pueraria lobata and exhibits a broad range of pharmacological activities. However, poor water solubility and low bioavailability limit its use. Enzymatic transglycosylation is emerging as a new strategy to improve the pharmacodynamic and pharmacokinetic properties of natural products for drug development. In this study, three PU glucosides (PU-G, PU-2G, and PU-3G) were synthesized by using a cyclodextrin glucanotransferase from Bacillus licheniformis with PU as the acceptor and α-cyclodextrin as the sugar donor. The transglycosylation products were isolated and structurally identified by mass spectrometry and nuclear magnetic resonance. The water solubilities of PU-G, PU-2G, and PU-3G were 15.6, 100.9, and 179.1 times higher than that of PU, respectively. Moreover, the antiosteoporosis activities of these glucosides were tested, and PU-G was found to show much more potent antiosteoporosis activity as compared to the original PU.

Medicinal plants are a vital source of natural products (NPs) that can cure cancer through modulation of different pathways, including oxidative stress, extrinsic and intrinsic apoptosis, cell cycle, inflammation, NF-kB, PI3K/AKT/mTOR, AMPK (JNK), MEK/ERK (Raf)-MEK-ERK and autophagy. Puerarin (Pue), an important NP belonging to the isoflavone glycoside group, is derived from Pueraria lobata (Willd.) Ohwi, Pueraria thomsonii Benth, and Pueraria tuberosa (Willd.). This NP was approved by the Chinese Ministry of Health for the treatment of different diseases in 1993, but it was also later reported to exhibit anticancer activity. Pue causes cancer cells death through modulation of different mechanisms including oxidative stress, intrinsic and extrinsic, Survivin and XIAP, PI3K/AKT/mTOR, Ras-Raf-MEK-ERK, JNK, cell cycle, AMPK, NF-kB, inflammation and autophagy pathways. Therefore, this review compiles for the first time the studies about the anticancer mechanism of Pue and provides comprehensive information about the anticancer effects of Pue. This review may serve as a basis for future research and clinical treatment.

The clinical and experimental study into the effects of Chinese herbal medicines on chronic kidney disease has evolved over the past 40 years with new insight into their mechanism and evidence of their clinical effects. Among the many traditional Chinese herbs examined in chronic renal disease, five were found to have evidence of sufficient clinical efficacy, high frequency of use, and well-studied mechanism. They are: Abelmoschus manihot and Huangkui capsule, Salvia miltiorrhiza and its components (tanshinone II A, salvianolic acid A and B); Rhizoma coptidis and its monomer berberine; Tripterygium wilfordii and its components (triptolide, tripterygium glycosides); Kudzu root Pueraria and its monomer Puerarin. These Chinese herbal medications have pharmaceutical effects against fibrosis, inflammation and oxidative stress and also promote renal repair and regeneration. This article reviews their clinical efficacy, anti-fibrotic effects in animal models, and molecular mechanism of action.

Kudzu, Pueraria lobata, is a traditional Chinese food and medicinal herb that has been commonly used since ancient times. Kudzu roots are rich sources of isoflavonoids, e.g., puerarin, with beneficial effects on human health. To gain global information on the isoflavonoid biosynthetic regulation network in kudzu, de novo transcriptome sequencings were performed using two genotypes of kudzu with and without puerarin accumulation in roots. RNAseq data showed that the genes of the isoflavonoid biosynthetic pathway were significantly represented in the upregulated genes in the kudzu with puerarin. To discover regulatory genes, 105, 112, and 143 genes encoding MYB, bHLH, and WD40 transcription regulators were identified and classified, respectively. Among them, three MYB, four bHLHs, and one WD40 gene were found to be highly identical to their orthologs involved in flavonoid biosynthesis in other plants. Notably, the expression profiles of PlMYB1, PlHLH3-4, and PlWD40-1 genes were closely correlated with isoflavonoid accumulation profiles in different tissues and cell cultures of kudzu. Over-expression of PlMYB1 in Arabidopsis thaliana significantly increased the accumulation of anthocyanins in leaves and proanthocyanidins in seeds, by activating AtDFR, AtANR, and AtANS genes. Our study provided valuable comparative transcriptome information for further identification of regulatory or structural genes involved in the isoflavonoid pathway in P. lobata, as well as for bioengineering of bioactive isoflavonoid compounds.

In this work, we discovered a new fermentation broth that can prevent and regulate alcoholic liver disease (ALD) and intestinal flora, which fermented the mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1. The contents of polyphenols, puerarin, total isoflavones, and amino acids were significantly increased. Animal experiments showed that the fermentation broth could improve the liver indexes of ALD mice model, increase the activity of superoxide dismutase and glutathione in liver tissue, and reduce the level of malondialdehyde (MDA). Furthermore, the fermentation broth can reduce the levels of serum lipopolysaccharide (LPS), inflammatory factors interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Importantly, intestinal flora analysis showed that the fermentation broth could increase the abundance of Lactobacillales and reduce the production of Gram-negative bacteria, thereby reducing the abnormal increase in bacterial diversity caused by alcohol. In conclusion, we may have discovered a new functional food raw material with great application potential. The above findings indicate that the fermentation broth can actively regulate the intestinal flora and improve liver inflammation. The underlying mechanism might be that the fermentation broth could enhance intestinal permeability and reduce the inflammatory signals and LPS transmitted through the gut-liver axis, thereby reducing the oxidative stress and inflammation of the liver caused by alcohol.

Diabetes mellitus (DM), as a chronic disease caused by insulin deficiency or using obstacles, is gradually becoming a principal worldwide health problem. Pueraria lobata is one of the traditional Chinese medicinal and edible plants, playing roles in improving the cardiovascular system, lowering blood sugar, anti-inflammation, anti-oxidation, and so on. Studies on the hypoglycemic effects of Pueraria lobata were also frequently reported. To determine the active ingredients and related targets of Pueraria lobata for DM, 256 metabolites were identified by LC/MS non targeted metabonomics, and 19 active ingredients interacting with 51 DM-related targets were screened. The results showed that puerarin, quercetin, genistein, daidzein, and other active ingredients in Pueraria lobata could participate in the AGE-RAGE signaling pathway, insulin resistance, HIF-1 signaling pathway, FoxO signaling pathway, and MAPK signaling pathway by acting on VEGFA, INS, INSR, IL-6, TNF and AKT1, and may regulate type 2 diabetes, inflammation, atherosis and diabetes complications, such as diabetic retinopathy, diabetic nephropathy, and diabetic cardiomyopathy.

In diabetic patients, high glucose and high oxidative states activate gene expression of transforming growth factor beta (TGF-β) and further translocate Smad proteins into the nucleus of renal cells. This signal pathway is characterized as the onset of diabetic nephropathy. Puerarin is an active ingredient extracted from Pueraria lobata as an anti-hyperglycemic and anti-oxidative agent. However, the poor oral availability and aqueous solubility limit its pharmaceutical applications. The present paper reports the liposomal puerarin and its protective effect on high glucose-injured rat mesangial cells (RMCs). The purity of puerarin extracted from the root of plant Pueraria lobata was 83.4% as determined by the high-performance liquid chromatography (HPLC) method. The liposomal puerarin was fabricated by membrane hydration followed by ultrasound dispersion and membrane extrusion (pore size of 200 nm). The fabricated liposomes were examined for the loading efficiency and contents of puerarin, the particle characterizations, the radical scavenge and the protective effect in rat mesangial cells, respectively. When the liposomes were subjected to 20 times of membrane extrusion, the particle size of liposomal puerarin can be reduced to less than 200 nm. When liposomal puerarin in RMCs in high glucose concentration (33 mM) was administered, the over-expression of TGF-β and the nuclear translocation of Smad 2/3 proteins was both inhibited. Therefore, this study successfully prepared the liposomal puerarin and showed the cytoprotective effect in RMCs under high glucose condition.

Background Puerarin exerts therapeutic effect on osteoporosis due to its inhibitory effect on the formation of osteoclasts. Puerarin is also widely established as an autophagy inhibitor. The study aimed to investigate the significance of autophagy in Puerarin-treated osteoclast formation. Methods Osteoclast precursors (OCPs) derived from bone marrow-derived macrophages (BMMs) were treated with Puerarin along with RANKL or without RANKL, and then the autophagic parameters of OCPs (including autophagic proteins, LC3 transformation, autophagosome or LC3-puncta) were observed through Western Blotting, Transmission Electron Microscopy and Immunofluorescence assays. Next, after using overexpression vectors of autophagic genes (Atg7, Atg5 and BECN1) to alter autophagy activity, OCP proliferation was measured by Ethynyl deoxyuridine (EdU) assays and Cell Counting Kit-8 (CCK-8) kit, and osteoclast differentiation was assessed by Tartrate-resistant acid phosphatase (TRAP) staining. Results The results showed that Puerarin could directly inhibit the autophagy and proliferation of OCPs. Importantly, overexpression of autophagic genes Atg5, Atg7 and BECN1 reversed Puerarin-inhibited OCP autophagy and proliferation. What’s more, RANKL could promote the autography of OCPs, which was recovered by Puerarin treatment. Interestingly, different from single-Puerarin treatment, we found that in the presence of RANKL, only BECN1 overexpression significantly reversed Puerarin-inhibited osteoclast differentiation and OCP autophagy. Conclusion In conclusion, Puerarin could inhibit the OCP autophagy in the presence or absence of RANKL, which blocked the OCP proliferation and osteoclast differentiation respectively. Moreover, BECN1 plays an essential role in Puerarin-inhibited osteoclastogenesis. Our study provides potential clue to further complete the intrinsic mechanism of Puerarin in treating osteoporosis.

Pueraria lobata (Willd.) Ohwi is a medicinal and edible homologous plant with a long history in China. Puerarin, the main component isolated from the root of Pueraria lobata, possesses a wide range of pharmacological properties. Daidzein and glucuronides are the main metabolites of puerarin and are excreted in the urine and feces. As active substrates of P-gp, multidrug resistance-associated protein and multiple metabolic enzymes, the pharmacokinetics of puerarin can be influenced by different pathological conditions and drug-drug interactions. Due to the poor water-solubility and liposolubility, the applications of puerarin are limited. So far, only puerarin injections and eye drops are on the market. Recent years, researches on improving the bioavailability of puerarin are developing rapidly, various nanotechnologies and preparation technologies including microemulsions and SMEDDS, dendrimers, nanoparticles and nanocrystals have been researched to improve the bioavailability of puerarin. In order to achieve biocompatibility and desired activity, more effective quality evaluations of nanocarriers are required. In this review, we summarize the pharmacokinetics and drug delivery systems of puerarin up to date.

Background: Recent studies indicate that vascular complications are closely related to diabetes mellitus; in particular, inflammatory-mediated endothelial dysfunction plays a crucial role in diabetes-induced cardiovascular diseases. Therefore, exploring effective methods to suppress endothelial dysfunction via inhibition of inflammatory responses is imperative. Puerarin (Pu), a flavonoid common in Pueraria, has been widely and successfully used to treat cardiovascular diseases in China for many years. However, information on its protective properties in hyperglycemia-induced vascular complications is insufficient. Hypothesis/Purpose: In this study, we investigate the protective effects of puerarin against high glucose-induced endothelial dysfunction and the underlying mechanism of the flavonoid. Methods: we investigated the protective effects of Pu against hyperglycemia-induced inter-endothelial junction by permeability and transendothelial electrical resistance (TEER) assay. In addition, changes in the Nlrp3 inflammasome activation via reactive oxygen species (ROS)-dependent oxidative pathway were investigated using western blot, immunofluorescence microscopy analyses and flow cytometry. ROS scavenger and Nlrp3 gene silencing were used to determine the roles of the ROS-Nlrp3 pathway involved in the molecular mechanism of Pu. Results: Our findings demonstrate that puerarin inhibits high glucose-induced Nlrp3 inflammasome formation and activation, as shown by fluorescence confocal microscopy and Western blot. Puerarin decreases Nlrp3 protein, which is a critical factor necessary to form an inflammasome complex. We demonstrate that puerarin exerts anti-oxidation and ROS scavenged effects, similar to apocynin (APO). Interestingly, thioredoxin-interacting protein (TXNIP) protein and TXNIP binding to Nlrp3 markedly decreased with puerarin treatment. Together with these changes, puerarin could decrease high mobility group box 1 (HMGB1) release from mouse vascular endothelial cell (mMVECs). We also demonstrate the decreased expression of the tight junction proteins ZO-1/ZO-2, which are related to endothelial permeability after stimulation by high glucose in endothelial cells. Puerarin could recover the gap junction protein and decrease monolayer cell permeability in endothelial cells. In conclusion, we reveal a new protection mechanism of puerarin that inhibits Nlrp3 inflammasome activation and decreases subsequent caspase-1 activation, triggering the release of HMGB1 by reducing ROS generation. Conclusions: Our findings indicate that puerarin exhibits immense potential and specific therapeutic value in hyperglycemia-related cardiovascular disease and the development of innovative drugs.

Puerarin, isolated from the roots of Pueraria lobata, is widely used for treating cerebral ischemia in China. The time- and dose-dependent distribution characteristics of puerarin in the ischemic hippocampus are unknown. In this study, puerarin concentration was determined by an indirect competitive ELISA using anti-puerarin monoclonal antibody. Area under the curve (AUC0-120 min) of puerarin (80 mg/kg) in the embolic hippocampus was higher than that in the normal hippocampus; the increase was significant only at 40 and 20 mg/kg. The maximum concentration (Cmax) of puerarin in the embolic hippocampus was higher than that in the normal hippocampus at all doses. The increase in both AUC0-120 min and Cmax was dose-dependent. Time to reach the maximum concentration (Tmax) of puerarin in the embolic and normal hippocampus was similar. Although the mean residence time in the embolic hippocampus differed from that in the normal hippocampus at 40 and 80 mg/kg, it was higher in the embolic hippocampus than in the normal hippocampus at 20 mg/kg. This is the first study to report that the time- and dose-dependent distribution characteristics of puerarin in the normal and embolic hippocampus after middle cerebral artery occlusion in rats dictate puerarin dose and duration to treat stroke.

Puerariae Radix (PR) and Gastrodiae Rhizome (GR) is frequently used in traditional herbal formulas to treat cardio-cerebral vascular diseases due to their synergistic effects. In this study, to elucidate the action mechanism of PR-GR in vivo, a simple and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of nine bioactive ingredients from PR-GR in plasma was developed and applied to a comparative pharmacokinetic study following oral administration of PR, GR, and PR-GR aqueous extracts in rats. The effect of GR on the absorption of components of PR was also investigated by single-pass intestinal perfusion study. Results showed that comparing to the single herbs, PR-GR extract significantly increased the systemic exposure of puerarin, 3'-hydroxypuerarin, 3'-methoxypuerarin, 6″-O-xylosylpuerarin, daidzin, genistein, and gastrodin. Moreover, the intestinal absorption of puerarin and daidzin could be improved by GR extract and inhibitors of P-glycoprotein and multidrug resistanceassociated protein 2, respectively. These results indicate that the combination of PR and GR increases the levels of their bioactive ingredients exposed in the blood, and GR increases the absorption of ingredients of PR may by inhibition of the efflux mediated by P-glycoprotein and multidrug resistanceassociated protein 2. This is the first report for the pharmacokinetics and intestinal absorption of PR-GR, which may explain their synergetic effects in the treatment of circulatory systematic diseases and provide a meaningful insight for their clinical applications.

Background Puerarin, derived from a traditional Chinese herb Pueraria lobata (Willd.) Ohwi which was distributed globally and planted in most parts of China, has been extensively applied in patients with cardiovascular diseases in China. Yet a considerable proportion of the patients were accompanied with liver illnesses simultaneously because of all sorts of reasons. Hypothesis/Purpose It had been implied by some previous research that the absorption and the metabolism of puerarin were susceptible to liver issues due to changed P-gp and Ugt1a level, but pharmacokinetics of puerarin under such conditions were few concerned. Our study aimed to make sure whether and how much the behavior of puerarin in vivo was affected by hepatic diseases, and to explore the potential mechanisms. Methods A CCl4 induced rat model of hepatic fibrosis (HF) was prepared and verified. Single low/high doses of oral and intravenous administration of puerarin to HF and normal rats were performed. Pharmacokinetics of puerarin were determined by a validated HPLC method. The expression of P-gp, Ugt1a1, and Ugt1a7 in both liver and intestines were determined by quantitative RT-PCR and Western blot analysis respectively. Results The systemic exposure of puerarin in HF rats of experimental groups were found decreased remarkably except for that of the high dose intravenous group. Moreover, the expression of P-gp, Ugt1a1, and Ugt1a7 in liver and intestines of HF rats were figured out increased. Conclusion The results indicated that the HF originated overexpression of Ugt1a1, Ugt1a7, and P-gp level played important roles in pharmacokinetics of puerarin, suggested the clinical regimen of puerarin based on normal populations might be inappropriate for patients with chronic liver diseases. It was implied drugs whose absorption or elimination were related to P-gp, Ugt1a1, or Ugt1a7 might also be affected by hepatic illnesses.

Diabetes mellitus (DM) remains a great challenge in treatment due to pathological complexity. It has been proven that phytomedicines and natural medicines have prominent antidiabetic effects. This work aimed to develop selenium-layered nanoparticles (SeNPs) for oral delivery of mulberry leaf and Pueraria Lobata extracts (MPE), a group of phytomedicines with significant hypoglycemic activities, to achieve a synergic antidiabetic effect. MPE-loaded SeNPs (MPE-SeNPs) were prepared through a solvent diffusion/in situ reduction technique and characterized by particle size, ζ potential, morphology, entrapment efficiency (EE) and drug loading (DL). The resulting MPE-SeNPs were 120 nm around in particle size with EE of 89.38% for rutin and 90.59% for puerarin, two marker components in MPE. MPE-SeNPs exhibited a slow drug release and good physiological stability in the simulated digestive fluid. After oral administration, MPE-SeNPs produced significant hypoglycemic effects both in the normal and diabetic rats. Ex vivo intestinal imaging and cellular examinations demonstrated that MPE-SeNPs were provided with outstanding intestinal permeability and transepithelial transport aptness. It was also revealed that MPE-SeNPs could alleviate the oxidative stress, improve the pancreatic function, and promote the glucose utilization by adipocytes. Our study provides new insight into the use of integrative nanomedicine containing phytomedicines and selenium for DM treatment., Graphical abstract Selenium-layered nanoparticles (SeNPs) were developed by self-assembly/in situ reduction technique to orally deliver mulberry leaf and Pueraria Lobata extracts (MPE) and enhanced antidiabetic efficacy was achieved through the synergy between selenium and hypoglycemic phytomedicines.fx1

The root of Pueraria lobata has been utilized as a food source for thousands of years in China. Puerarin is the major bioactive and the most abundant secondary metabolite obtained from the root of P. lobata. The potential therapeutic effect of puerarin against Alzheimer's disease was screened by in silico methods and confirmed by the amyloid β-peptide-induced Alzheimer's disease (AD) rat model. The in silico study displayed that puerarin had the potential to penetrate across the blood-brain barrier and had high stability in molecular docking and dynamics simulation with acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2) and caspase-3 (C3), which play a central role in the development of AD. The in vivo results showed that puerarin could restrain the AChE activity, restore the activities of antioxidant defense substances toward normal levels, and decrease the expression of inflammatory factors and apoptosis genes in the brain, especially down-regulating the expressions of COX-2 and C3. The histopathological examination of brain sections and behavioral testing also verified the biochemical observations, which further validates the in silico study. These results not only suggest that puerarin, as a potential compound, could relieve AD, but also broaden the applications of puerarin.

Puerarin is an isoflavonoid isolated from the root of Pueraria lobata (Gegen in Chinese) that has been widely used to treat cardiovascular and cerebrovascular diseases in China. Here, we investigated the hypotensive effects and mechanisms of puerarin in spontaneously hypertensive rats. The qPCR array technique was used to determine the expression of hypertension-related genes. Then, the differentially expressed genes were analyzed using the STRING database. The systolic blood pressure and diastolic blood pressure of rats decreased after the administration of puerarin for nine weeks. Puerarin, but not losartan, also slowed the heart rate of rats. NO and cGMP levels were improved by puerarin. Eighteen differentially expressed hypertension-related genes were identified by comparing the model group with the control group and the high-dose puerarin group with the model group. NO and cGMP levels were increased by high-dose puerarin. High-dose puerarin increased the levels of the phosphorylated eNOS protein and decreased AT1 and Cav1 levels. Based on our results, eNOS was a key target in the mechanism by which puerarin reduced blood pressure, and puerarin represents a potential antihypertensive agent.

Pueraria, a Chinese herbal medicine, plays an important role in many classic prescriptions for the treatment of diabetes. Puerarin is the main component of pueraria. The current in vivo and in vitro research mainly focus on exploring the potential mechanism of puerarin in inhibiting hepatic gluconeogenesis. The type 2 diabetic rats were established by a combination of small dosage of streptozotocin (STZ) injection with high-fat diet. After the administration of puerarin 4 weeks, the parameters of the glucose and lipid metabolism were determined. HepG2 cells were treated by palmitic acid (PA) to induce the insulin resistance in vitro model. After the treatment of puerarin, the glucose consumption and cell viability were examined. Then, the protein expression of PI3K, Akt, pAkt, pFOXO1, FOXO1, PEPCK and G6pase in liver tissue and HepG2 cells were evaluated by western blot. RT-PCR was used to measure the content of PEPCK, G6pase mRNA in liver tissue. The results showed that puerarin administration significantly decrease the level of FBG, HbA1C and triglycerides in diabetic rats. Mechanistic research showed that puerarin activating PI3K/Akt is puerarin-mediated beneficial effects and can be reversed by inhibitor of PI3K or Akt. In conclusion, puerarin inhibits hepatic gluconeogenesis by activating PI3K/Akt signaling pathway.

Exessive drinking is commonly associated with a wide spectrum of liver injuries. The term alcoholic liver disease (ALD) is generally used to refer to this spectrum of hepatic abnormalities, and the term hepatic steatosis denotes early lesions. Puerariae Lobatae Radix (PLR) is a common traditional Chinese medicine and has been widely used as an efficient treatment for alcohol-induced damage. Flavonoids are the principal components of PLR that could potentially be responsible for the activation of alcohol metabolism and lipid-lowering effects. However, little is known about the mechanisms underlying their activity against alcoholic injury. In this study, PLR flavonoids (PLF) were obtained by microwave extraction. A 2% ethanol solution was used to establish a model of alcoholic fatty liver disease by exposure of zebrafish larvae for 32 h, and then the zebrafish were administered PLF and puerarin. The results showed that PLF and puerarin significantly decreased lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Moreover, PLF and puerarin downregulated the expression of genes related to alcohol and lipid metabolism (CYP2y3, CYP3a65, ADH8a, ADH8b, HMGCRB, and FASN), endoplasmic reticulum stress, and DNA damage (CHOP, EDEM1, GADD45αa, and ATF6) and reduced levels of inflammatory factors (IL-1β, TNF-α) in zebrafish larvae. PLF and puerarin increased the phosphorylation of AMP-activated protein kinase-α (AMPKα) and decreased the total protein level of ACC1. The findings suggested that PLF and puerarin alleviated alcohol-induced hepatic steatosis in zebrafish larvae by regulating alcohol and lipid metabolism, which was closely related to the regulation of the AMPKα-ACC signaling pathway. In conclusion, the study provided a possible therapeutic drug for ALD treatment.

Objective. Depression is a common mental disease with long course and high recurrence rate. Previous studies showed that Puerariae Radix and its extracts have powerful antidepressant effects in recent years. The study proposed an integrated strategy, combining network pharmacology and molecular pharmacology experiment to investigate the mechanisms of the antidepressant active ingredients from Puerariae Radix. Methods. TCMSP database, GeneCards database, Venny 2.1, UniProt database, STRING database, Cytoscape 3.7.2, and Metascape database were used to screen the active chemical components, antidepressant-related genes, and core targets, convert the abbreviated gene names in batch, search and predict the interaction between proteins, and construct the PPI network of Puerariae Radix. KEGG pathway and GO biological process enrichment and biological annotation were used to select antidepressant core gene targets. The MTT method was used to detect the effect of puerarin on the damage of PC12 cells induced by corticosterone. The DCFH-DA probe and ROS assay kit were utilized to detect the production of ROS in PC12 cells. PI/Annexin V was used to detect the apoptotic rate of puerarin on PC12 cells. Western blotting was used to verify the regulation of puerarin on the key targets of AKT1, FOS, CASP3, STAT3, and TNF-α in PC12 cells. Results and Conclusion. Eight main active components, 64 potential antidepressant gene targets, and 15 core antidepressant gene targets were obtained. 35 signaling pathways and 52 biological processes related to antidepressant effect of Puerariae Radix were identified. Puerarin was the active ingredient derived from Puerariae Radix which exhibited the antidepression effect by improving the viability of cell, reducing cell apoptosis, regulating ROS production, increasing protein expressions of AKT1 and FOS, and reducing protein expressions of CASP3, STAT3, and TNF-α. The study revealed the pharmacodynamic material basis and possible antidepressant mechanism of Puerariae Radix and provided new theoretical basis and ideas for antidepressant research.

Pueraria thomsonii Benth. (P. thomsonii) and Pueraria lobata (willd.) Ohwi. (P. lobata) are two members of the genus Pueraria, which have been widely used as medical herb and nutrition supplement in Asia. However, these two herbs share the same descriptions in pharmacological activities in Chinese Pharmacopeia, and are used interchangeably in applications. Differentiating the pharmaceutical applications and nutritional properties of two species of pueraria. Comparatively analysing the differences in the chemical composition and bioactivity of the two types of pueraria, then illustrating their applications. Metabolomics-based methods were established to identify the chemical constituents using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The contents of total flavonoids and four kinds of saccharides were evaluated separately by spectrophotometry methods. Their biological activities on hypoxia-reoxygenation (H/R) H9c2 cells were further assessed with cell viability by methyl thiazolyl tetrazolium (MTT) assay. Bio-active compounds including puerarin, daidzin, genistin etc. were significantly enriched in P. lobata, which was accountable for its protective effect on cardiocytes. P. thomsonii contained more saccharides and was not cardioprotective in H/R injury. The study indicates different contents of chemical constituents and biological activities between these two species of pueraria. Therefore, P. lobata is suitable for medicinal products, while P. thomsonii presents more value for use in nutritional food.

Natural deep eutectic solvent (NaDES) is generally considered as a greener alternative to fossil solvent, with great potential in various areas. In the present work, 25 different NaDESs were screened for the extraction of puerarin (PUE) and its two natural derivatives from Radix Pueraria (RP). As the main isoflavone in RP, PUE has a wide range of biological activities. However, its application is restricted due to its poor solubility in water and low oral bioavailability. In this study, the extraction of PUE with NaDESs showed significant advantages compared with traditional solvents. While using L-Pro-Maa (L-proline-malic acid) under optimal conditions, the optimized yields of PUE, 3-MPR and PRX were 98.7 mg/g, 16.3 mg/g and 9.9 mg/g, respectively, which were 2.2-, 2.9- and 3.4-fold higher than that of water. Furthermore, the oral bioavailability of PUE in NaDES extracts was comparatively investigated in rats with HPLC-MS technique. Pharmacokinetic analysis revealed that the relative bioavailability of PUE in L-Pro-Maa extract is 323%. The result indicated that NaDES is not only a sustainable ionic liquid with higher extraction efficiency, but also an enhancer of oral bioavailability of specific natural products.