Revisiting Structure-activity Relationships: Unleashing the potential of selective Janus kinase 1 inhibitors.

Janus kinases (JAKs), a kind of non-receptor tyrosine kinases, the function has been implicated in the regulation of cell proliferation, differentiation and apoptosis, immune, inflammatory response and malignancies. Among them, JAK1 represents an essential target for modulating cytokines involved in inflammation and immune function. Rheumatoid arthritis, atopic dermatitis, ulcerative colitis and psoriatic arthritis are areas where approved JAK1 drugs have been applied for the treatment. In the review, we provided a brief introduction to JAK1 inhibitors in market and clinical trials. The structures of high active JAK1 compounds (IC50 ≤ 0.1 nM) were highlighted, with primary focus on structure-activity relationship and selectivity. Moreover, the druggability processes of approved drugs and high active compounds were analyzed. In addition, the issues involved in JAK1 compounds clinical application as well as strategies to surmount these challenges, were discussed.

[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

Phylogeography of cultivated and wild ophiopogon japonicus based on chloroplast DNA: exploration of the origin and sustainable cultivation.

BACKGROUND: Ophiopogon japonicus, mainly planted in Sichuan (CMD) and Zhejiang (ZMD) province in China, has a lengthy cultivation history. During the long period of domestication, the genetic diversity of cultivated O. japonicus has substantially declined, which will affect the population continuity and evolutionary potential of this species. Therefore, it is necessary to clarify the phylogeography of cultivated O. japonicus to establish a theoretical basis for the utilization and conservation of the genetic resources of O. japonicus. RESULT: The genetic diversity and population structure of 266 O. japonicus individual plants from 23 sampling sites were analyzed based on 4 chloroplast DNA sequences (atpB-rbcL, rpl16, psbA-trnH and rpl20-5'rps12) to identify the effects of domestication on genetic diversity of cultivars and determine their geographic origins. The results showed that cultivated O. japonicus and wild O. japonicus had 4 and 15 haplotypes respectively. The genetic diversity of two cultivars (Hd = 0.35700, π = 0.06667) was much lower than that of the wild populations (Hd = 0.76200, π = 0.20378), and the level of genetic diversity in CMD (Hd = 0.01900, π = 0.00125) was lower than that in ZMD (Hd = 0.06900, π = 0.01096). There was significant difference in genetic differentiation between the cultivated and the wild (FST = 0.82044), especially between the two cultivars (FST = 0.98254). This species showed a pronounced phylogeographical structure (NST > GST, P < 0.05). The phylogenetic tree showed that the genetic difference between CMD and ZMD was not enough to distinguish the cultivars between the two producing areas by using O. amblyphyllus Wang et Dai as an outgroup. In addition, both CMD and ZMD have a closer relationship with wild populations in Sichuan than that in Zhejiang. The results of the TCS network and species distribution model suggested that the wild population TQ located in Sichuan province could serve as the ancestor of cultivated O. japonicus, which was supported by RASP analysis. CONCLUSION: These results suggest that cultivated O. japonicus has experienced dramatic loss of genetic diversity under anthropogenic influence. The genetic differentiation between CMD and ZMD is likely to be influenced by founder effect and strong artificial selection for plant traits. It appears that wild populations in Sichuan area are involved in the origin of not only CMD but also ZMD. In addition, we also raise some suggestions for planning scientific strategies for resource conservation of O. japonicus based on its genetic diversity and population structure.

Mechanisms of Epichloë bromicola to Promote Plant Growth and Its Potential Application for Coix lacryma-jobi L. Cultivation.

Endophytic fungi play important roles in regulating plant growth and development and usually used as a promising strategy to enhance the biosynthesis of host valuable secondary metabolite, but the underlying growth-promoting mechanisms are only partly understood. In this study, the wild-type Arabidopsis thaliana seedlings co-cultured with fungal endophyte Epichloë bromicola showed auxin (IAA)-stimulated phenotypes, and the growth-promoting effects caused by E. bromicola were further verified by the experiments of spatially separated co-culture and fungal extract treatment. IAA was detected and identified in the extract of E. bromicola culture by LC-HRMS/MS, whereas 2,3-butanediol was confirmed to be the predominant volatile active compound in the diethyl ether and ethyl acetate extracts by GC-MS. Further study observed that IAA-related genes including synthesis key enzyme genes (CYP79B2, CYP79B3, NIT1, TAA1 and YUCCA1) and controlling polar transport genes (AUX1, BIG, EIR1, AXR3 and ARF1), were highly expressed at different periods after E. bromicola inoculation. More importantly, the introduction of fungal endophyte E. bromicola could effectively promote the growth and accumulation of coixol in Coix under soil conditions. Our study showed that endophytic fungus E. bromicola might be considered as a potential inoculant for improving medicinal plant growth.

[Chemical constituents, pharmacological activities, processing and clinical application of traditional Chinese medicine Scrophulariae Radix: a review].

Traditional Chinese medicine Scrophulariae Radix, which is also called Yuan Shen, black Shen, is the dried root of Scrophularia ningpoensis of the Scrophulariaceae family. Research has indicated that the chemical constituents of Scrophulariae Radix mainly include terpenoids, phenylpropanoids, organic acids, volatile oils, steroids, sugars, flavonoids, alkaloids and phenols, among which iridoids and phenylpropanoids were the main active constituents. It has been reported that extracts of Scrophulariae Radix or its active substances have anti-inflammatory, antioxidant, hepatoprotective, anti-tumor, anti-fatigue, uric acid-lowering, anti-depression, myocardial cell-protective and other pharmacological activities, and can regulate cardiovascular system, central nervous system and immune system. This paper reviewed the present research achievements of Scrophulariae Radix in chemical constituents, pharmacological activities, processing methods, toxicity and other aspects, and the clinical application of Scrophulariae Radix in ancient and modern times was illustrated. This paper aimed to provide reference for further research of Scrophulariae Radix and facilitated its clinical application.

[Research progress on anti-inflammatory effects of plant-derived cannabinoid type 2 receptor modulators].

Excessive and persistent inflammatory responses are a potential pathological condition that can lead to diseases of various systems, including nervous, respiratory, digestive, circulatory, and endocrine systems. Cannabinoid type 2 receptor(CB2R) belongs to the G protein-coupled receptor family and is widely distributed in immune cells, peripheral tissues, and the central nervous system. It plays a role in inflammatory responses under various pathological conditions. The down-regulation of CB2R activity is an important marker of inflammation and and CB2R modulators have been shown to have anti-inflammatory effects. This study explored the relationship between CB2R and inflammatory responses, delved into its regulatory mechanisms in inflammatory diseases, and summarized the research progress on CB2R modulators from plants other than cannabis, including plant extracts and monomeric compounds, in exerting anti-inflammatory effects. The aim is to provide new insights into the prevention and treatment of inflammatory diseases.

Transcriptome sequencing and signal transduction for the enhanced tanshinone production in Salvia miltiorrhiza hairy roots induced by Trichoderma atroviride D16 polysaccharide fraction.

Salvia miltiorrhiza Bunge. is commonly used to treat vascular diseases because of its activity ingredients, phenolic acids, and tanshinones. Polysaccharide fraction (PSF) extracted from Trichoderma atroviride D16 could promote tanshinone accumulation in S. miltiorrhiza hairy roots. Transcriptome sequencing was conducted to describe the global gene expression of PSF-treatment hairy roots, and data analyses showed enzymes of tanshinone biosynthetic pathways were up-regulated, and genes associated to signal molecules and transcription factors were responsive. Endogenous H2O2, abscisic acid, and nitric oxide contents were measured after PSF treatment, while tanshinone accumulations were measured with treatment of exogenous H2O2 or H2O2 inhibitor on PSF-treatment S. miltiorrhiza hairy roots. The results showed H2O2 was important in tanshinone biosynthesis caused by PSF and nitric oxide might be the downstream molecules of H2O2. Taken together, the study indicates that D16 PSF enhances the accumulation of tanshinones through enzymes of tanshinone biosynthetic pathways, signal molecules, and transcription factors.

Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects.

As cannabinoid CB2 receptors (CB2R) possess various pharmacological effects-including anti-epilepsy, analgesia, anti-inflammation, anti-fibrosis, and regulation of bone metabolism-without the psychoactive side effects induced by cannabinoid CB1R activation, they have become the focus of research and development of new target drugs in recent years. The present study was intended to (1) establish a double luciferase screening system for a CB2R modulator; (2) validate the agonistic activities of the screened compounds on CB2R by determining cAMP accumulation using HEK293 cells that are stably expressing CB2R; (3) predict the binding affinity between ligands and CB2 receptors and characterize the binding modes using molecular docking; (4) analyze the CB2 receptors-ligand complex stability, conformational behavior, and interaction using molecular dynamics; and (5) evaluate the regulatory effects of the screened compounds on bone metabolism in osteoblasts and osteoclasts. The results demonstrated that the screening system had good stability and was able to screen cannabinoid CB2R modulators from botanical compounds. Altogether, nine CB2R agonists were identified by screening from 69 botanical compounds, and these CB2R agonists exhibited remarkable inhibitory effects on cAMP accumulation and good affinity to CB2R, as evidenced by the molecular docking and molecular dynamics. Five of the nine CB2R agonists could stimulate osteoblastic bone formation and inhibit osteoclastic bone resorption. All these findings may provide useful clues for the development of novel anti-osteoporotic drugs and help elucidate the mechanism underlying the biological activities of CB2R agonists identified from the botanical materials.

Development of hypothyroidism over 13 years of follow-up of patients with hyperthyroidism after radioiodine therapy.

OBJECTIVE: To analyze the incidence and associated factors of hypothyroidism after radioiodine treatment for hyperthyroidism during a 13-year follow-up period. SUBJECTS AND METHODS: This was a retrospective study of consecutive patients with hyperthyroidism who were treated using a single dose of radioactive iodine (RAI) with a calculated dose regimen from 07/2005 to 12/2012. Univariate and multivariate Cox regression models were used to examine the factors that are associated with the occurrence of hypothyroidism after RAI therapy. Kaplan-Meier analysis was used for confirming associations between these models. RESULTS: A total of 182 patients were included during a 7.5-year median follow-up (range: 6-13 years). They were 36.4±11.1 years. The mean radioactive iodine dosage was 308.2±104.3 (range: 129.5-740.0) MBq. The rates of euthyroidism, early hypothyroidism, improvement, and ineffective treatment at 6 months were 48.4%, 37.9%, 8.8%, and 4.9%, respectively. The cumulative incidence of hypothyroidism in all patients with hyperthyroidism was 45.6% at 1 year, 48.9% at 5 years, and 52.3% at 10 years. Thyroid weight >46g (HR=0.643, 95%CI: 0.422-0.981, P=0.040) and a course of disease of 0.5-3 years (HR=0.592, 95%CI: 0.358-0.981, P=0.042) were identified as independent factors associated with an increased risk of hypothyroidism after radioactive iodine therapy. CONCLUSION: Radioactive iodine treatment with a calculated dose has a high cure rate for hyperthyroidism and has a low annual increase of hypothyroidism. Hypothyroidism after radioactive iodine treatment is more likely to occur in patients with small thyroid and a short disease course.

[Genetic diversity and genetic structures of original plants of Viticis Fructus:an SSR markers-based analysis].

The present study aimed to provide the protection strategies for wild germplasm resources of original plants of Viticis Fructus and a theoretical basis for the sustainable use of Viticis Fructus. The genetic diversity and genetic structures of the 232 indivi-duals in 19 populations of Vitex rotundifolia and V. trifolia were analyzed by eight SSR markers with tools such as Popgene32, GenAlex 6.502, and STRUCTURE. Bottleneck effect was detected for the population with more than 10 individuals. The results indicated that 42 and 26 alleles were detected from the populations of V. rotundifolia and V. trifolia, respectively, with average expected heterozygo-sities of 0.448 6 and 0.583 9, which are indicative of low genetic diversity. AMOVA revealed the obvious genetic variation of V. rotundifolia and V. trifolia within population(84.43%, P<0.01; 60.37%, P<0.01). Furthermore, in eight SSR loci, six from V. rotundifolia populations and two from V. trifolia populations failed to meet Hardy-Weinberg equilibrium expectations(P<0.05), which confirmed that the populations experienced bottleneck effect. As assessed by Mantel test, geographical distance posed slight impacts on the genetic variation between the populations of V. rotundifolia and V. trifolia. Principal component analysis(PCA) and STRUCTURE analysis demonstrated evident introgression of genes among various populations. The original plants of Viticis Fructus were confirmed low in genetic diversity and genetic differentiation level. Therefore, the protection of wild resources of original plants of Viticis Fructus should be strengthened to ensure its sustainable use.

[Research progress on natural cannabinoid receptor type 2( CB2R)regulators and their effects on bone metabolism].

Cannabinoid receptor type 2( CB2 R),a member of the G protein-coupled receptor( GPCR) superfamily,has a variety of biological activities,such as regulating pain response,resisting inflammation and fibrosis,and mediating bone metabolism. Some CB2 R regulators exhibit a good regulatory effect on bone metabolism. Cannabinoids in Cannabis sativa can cause psychoactive effects despite various pharmacological actions they exerted by targeting CB2 R. Therefore,it is of great significance to discover CB2 R regulators in non-Cannabis plants for finding new lead compounds without psychoactive effects and elucidating the action mechanism of plant drugs. The present study clarifies the discovery,structure,and physiological functions of CB2 R,especially its regulatory effects on bone metabolism,summarized CB2 R regulators extracted from non-Cannabis plants,and systematically analyzes the regulatory effects of CB2 R regulators on bone metabolism in animals,osteoblasts,and osteoclasts,to provide a scientific basis for the discovery of new CB2 R regulators and the development of anti-osteoporotic drugs.

[Research progress on protective effect of traditional Chinese medicine and natural medicine on methotrexate-induced liver toxicity].

Methotrexate(MTX) is a commonly used antimetabolite, which can be used in the treatment of a variety of diseases. However, hepatotoxicity in the use of MTX severely limits its clinical use. Therefore, how to prevent and treat hepatotoxicity of MTX has become an urgent clinical problem. This paper summarizes and analyzes relevant literatures on the prevention and treatment of hepa-totoxicity caused by MTX with traditional Chinese medicines and natural medicines in recent years. MTX-induced hepatotoxicity mechanisms include folate pathway, oxidative stress damage and adenosine pathway, of which oxidative stress theory is the main research direction. A total of 14 kinds of traditional Chinese medicine and natural medicine extracts including white peony root, and 21 kinds of natural monomer compounds, including berberine, play an anti-MTX-induced hepatotoxic effect by resisting oxidative stress, inhibiting inflammation and regulating signal pathways. According to current studies on the prevention and treatment of hepatotoxicity induced by MTX with traditional Chinese medicines and natural medicines, there are insufficiencies, such as partial and superficial mechanism studies, inadequate combination of experimental research and clinical practice, non-standard experimental design and lack of application of advanced technologies and methods. This paper systematically reviewed the effects and mechanisms of traditional Chinese medicines and natural medicines against hepatotoxicity induced by MTX and defined current studies and deficiencies, in the expectation of proposing new study strategies and directions and providing scientific basis for rational clinical use of MTX and development of new drugs against MTX hepatotoxicity.

Apoptosis gene reprograming of human peripheral blood mononuclear cells induced by radioiodine-131 (131I) irradiation.

Background & objectives: The nature of adaptable change of B-cell lymphoma-2 (BCL-2) and/or Bcl2-associated X protein (BAX) gene expression in the human peripheral blood mononuclear cells (PBMCs) irradiated by radioiodine in thyroid diseases therapy is not fully understood. In this study, the alternation of apoptotic gene expression was evaluated while the PBMCs collected from healthy volunteers were irradiated by the radioiodine-131 (131I). Methods: Fasting blood samples were obtained from healthy volunteers. PBMCs from group 0 to 6 were incubated and exposed to different doses of 131I in cell suspension for 6, 12, 24 and 48 h. The apoptosis rates and expression of BCL-2 and BAX genes of PBMCs were examined. Results: The apoptosis rate in the human PBMCs was gradually enhanced after six hour irradiation. The values of BCL-2 and BAX gene expression in groups 1-6 were higher than in group 0 within 6 h of irradiation, and then, these were decreased gradually from 6 to 12 h. BCL: -2 gene expression increased in groups 1-3 after 12 h irradiation, but there was no difference in groups 4-6. The ratio of BCL-2/BAX gene expression among groups 4-6 gradually decreased during the period from 6 to 12 h, and it was significantly lower than in the group 0 at 12, 24 and 48 h. Interpretation & conclusions: The expression of BCL-2 and BAX genes was initially upregulated following irradiation. Later, the balance of BCL-2/BAX genes expression was adjusted, and then, PBMCs underwent apoptosis at higher doses of radiation.

[Isolation and identification of endophytic fungi producing harpagoside and harpagide from Scrophularia ningpoensis].

The endophytic fungi from root,main stem,branch and leaf of Scrophularia ningpoensis were isolated from Zhejiang,whether these strains could yield harpagide or harpagoside were tested by HPLC and LC-MS. According to the morphological characteristic and the similarity of the nucleotide sequence of internal transcribed spacer( ITS) between r DNAs,the strains producing harpagide or harpagoside were identified. The results showed that 210 strains were isolated from the samples,which were classified into 9 orders,13 families and 17 genera by morphological study. Harpagide was detected in endogenous fungi ZJ17 and harpagoside was detected in endogenous fungi ZJ25 by HPLC coupled with LC-MS. ZJ17 was identified as Alternaria alternate and ZJ25 was identified as A.gaisen by its morphology and authenticated by ITS( ITS4 and ITS5 regions and the intervening 5. 8 S rDNA region).

Rubiadin-1-methyl ether from Morinda officinalis How. Inhibits osteoclastogenesis through blocking RANKL-induced NF-κB pathway.

Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of Morinda officinalis How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from Morinda officinalis How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption.

The regulatory mechanism of fungal elicitor-induced secondary metabolite biosynthesis in medical plants.

A wide range of external stress stimuli trigger plant cells to undergo complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Throughout evolution, endophytic fungi, an important constituent in the environment of medicinal plants, have known to form long-term stable and mutually beneficial symbiosis with medicinal plants. The endophytic fungal elicitor can rapidly and specifically induce the expression of specific genes in medicinal plants which can result in the activation of a series of specific secondary metabolic pathways resulting in the significant accumulation of active ingredients. Here we summarize the progress made on the mechanisms of fungal elicitor including elicitor signal recognition, signal transduction, gene expression and activation of the key enzymes and its application. This review provides guidance on studies which may be conducted to promote the efficient synthesis and accumulation of active ingredients by the endogenous fungal elicitor in medicinal plant cells, and provides new ideas and methods of studying the regulation of secondary metabolism in medicinal plants.

[Research progress of chemical constituents and pharmacological activities in Humulus lupulus].

Hops, the female inflorescences of the hop plant (Humulus lupulus), are widely used in the brewing industry to add bitterness and aroma to beer. Combining with the relevant literature, the chemical composition(resinae, volatile oil, polyphenol and polysaccharide) in hops and their pharmacological effects are reviewed in this paper so as to present some sights for further application research and development.

Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds.

Plant endophytic fungi have been recognized as an important and novel resource of natural bioactive products, especially in anticancer application. This review mainly deals with the research progress on the production of anticancer compounds by endophytic fungi between 1990 and 2013. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. All strains of endophytes producing antitumor chemicals were classified taxonomically and the genera of Pestalotiopsis and Aspergillus as well as the taxol producing endophytes were focused on. Classification of endophytic fungi producing antitumor compounds has received more attention from mycologists, and it can also lead to the discovery of novel compounds with antitumor activity due to phylogenetic relationships. In this review, the structures of the anticancer compounds isolated from the newly reported endophytes between 2010 and 2013 are discussed including strategies for the efficient production of the desired compounds. The purpose of this review is to provide new directions in endophytic fungi research including integrated information relating to its anticancer compounds.

Medicinal plant cell suspension cultures: pharmaceutical applications and high-yielding strategies for the desired secondary metabolites.

The development of plant tissue (including organ and cell) cultures for the production of secondary metabolites has been underway for more than three decades. Plant cell cultures with the production of high-value secondary metabolites are promising potential alternative sources for the production of pharmaceutical agents of industrial importance. Medicinal plant cell suspension cultures (MPCSC), which are characterized with the feature of fermentation with plant cell totipotency, could be a promising alternative "chemical factory". However, low productivity becomes an inevitable obstacle limiting further commercialization of MPCSC and the application to large-scale production is still limited to a few processes. This review generalizes and analyzes the recent progress of this bioproduction platform for the provision of medicinal chemicals and outlines a range of trials taken or underway to increase product yields from MPCSC. The scale-up of MPCSC, which could lead to an unlimited supply of pharmaceuticals, including strategies to overcome and solution of the associated challenges, is discussed.

Phytochemical and Pharmacological Profiles of Three Fagopyrum Buckwheats.

The genus Fagopyrum (Polygonaceae), currently comprising 15 species of plants, includes three important buckwheat species: Fagopyrum esculentum (F. esculentum) Moench. (common buckwheat), Fagopyrum tataricum (F. tataricum) (L.) Gaertn. (tartary buckwheat) and Fagopyrum dibotrys (F. dibotrys) (D. Don) Hara. (perennial buckwheat), which have been well explored due to their long tradition of both edible and medicinal use. This review aimed to present an up-to-date and comprehensive analysis of the phytochemistry and pharmacology of the three Fagopyrum buckwheats. In addition, the scope for future research was also discussed. All available references included in this paper were compiled from major databases, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. A total of 106 compounds isolated from three Fagopyrum buckwheats can be mainly divided into six classes: flavonoids, phenolics, fagopyritols, triterpenoids, steroids and fatty acids. Flavonoids and phenolic compounds were considered to be the major active components. Considerable pharmacological experiments both in vitro and in vivo have validated that Fagopyrum buckwheats possess antitumor, anti-oxidant, anti-inflammatory, hepatoprotective, anti-diabetic activities, etc. All reported data lead us to conclude that Fagopyrum buckwheats have convincing medicinal potential. However, further research is needed to explore its bioactive constituents, the relationship to their structural activities and the molecular mechanisms of action.