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Abstract This study investigated the reproductive traits of the hermaphroditic four-finger threadfin, Eleutheronema tetradactylum, along the coasts of Thailand during January to December 2021. Fish samples were collected from Pattani Bay, Thailand to assess the sex ratio, gonadosomatic index (GSI), maturity stage and fecundity. Additional fish samples were also collected from other areas to evaluate the length and weight at first sex change (Ls50 and Ws50) and length at first maturity (Lm50). The overall sex ratio for male and female was 1:0.69 with male being predominant throughout the year. Threadfin fish spawn the whole year round with peaks during moderate rainy and heavy rainy seasons. Histological examination confirmed its protandrous hermaphrodite posing multiple spawning habits. The average fecundity was 1.85 × 105 ± 1.05 × 105 eggs and positively related with standard length, body weight, gonad weight, and egg diameter (p

Abstract The threadfin Eleutheronema are the important fishery resources in Indo-Pacific regions and classified as the endangered species with considerable conservation values. Their genetic diversity and population structure remain essentially unknown but are critical for the proper management and sustainable harvests of such important fisheries. Here, the mitochondrial DNA sequences of CO1 and 16s rRNA were determined from 75 individuals of Eleutheronema tetradactylum and 89 individuals of Eleutheronema rhadinum collected from different locations of South China Sea and Thailand coastal waters. Genetic diversity analysis revealed that both E. tetradactylum (Haplotype diversity, H = 0.105–0.211; Nucleotide diversity, π = 0.00017–0.00043) and E. rhadinum (H = 0.074–0.663, π = 0.00013–0.01088) had low diversity. Population structure analysis demonstrated the shallow genetic differentiation among the South China Sea populations. The limited communication between China and Thailand populations caused the high genetic differentiation in all groups due to the low dispersal ability. Reconstruction of CO1 phylogenetic relationships and demographic studies across Indo-West-Pacific regions provided strong evidence for a shared common origin or ancestor of E. tetradactylum and E. rhadinum. Eleutheronema rhadinum were further subdivided into two distinct genetic lineages, with Clade A dominantly distributing in Thailand and Malaysia and Clade B distributing in China coastal waters. Phenotypic divergence, characterized mainly by the depth of caudal peduncle and length of caudal peduncle, was also observed for all populations, which was possibly associated with specific local adaptations to environmental changes. Our study suggested a strong need for the development of proper fishery management strategies and conservation actions for the imperiled Eleutheronema species.

Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.

Abstract Background Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction containing Astragali Radix and Angelicae Sinensis Radix at a ratio of 5: 1, is prescribed for menopausal women. Flavonoids and its flavonoid glycosides are considered as the major active ingredients within the herbal decoction; however, their amount is not controllable during the preparation. Besides, the aglycons within DBT are believed to have better gut absorption and pharmacological efficacy. Methods The herbal extract of DBT was fermented with Lactobacillus plantarum. The amounts of flavonoid glucosides and its aglycones in the fermented product were analyzed by using UPLC-MS/MS. In addition, in vitro assays were employed to evaluate the efficacy of the fermented DBT in regulating the activities of α-glucosidase, α-amylase and lipase, as well as their antioxidant capacity (DPPH and T-AOC assays) and anti-glycation property (BSA-methylglyoxal, BSA-fructose, and arginine-methylglyoxal models). Results The fermentation of DBT with L. plantarum drove a completed conversion of calycosin-7-O-β-D-glucoside and ononin to calycosin and formononetin, respectively. The chemical transformation could be probably mediated by β-glycosidase within the fermented product. Several in vitro assays corresponding to anti-diabetic functions were compared between parental DBT against its fermented product, which included the activities against α-glucosidase, α-amylase and lipase, as well as anti-oxidation and anti-glycation. The fermented DBT showed increased activities in inhibiting α-glycosidase, suppressing DPPH radical-scavenging and anti-glycation, as compared to the original herbal product. Conclusion These results suggested that DBT being fermented with the probiotic L. plantarum could pave a new direction for fermentation of herbal extract, as to strengthen its pharmacological properties in providing health benefits.

Abstract Background Danggui Buxue Tang (DBT) is a historical Chinese herbal decoction, and which has more than 800 years of applications. This herbal decoction solely contains two materials: Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) at a weight ratio of 5:1. Clinically, DBT aims to improve anemia syndrome. In complementary and alternative medicine theory, the cause of neurodegenerative disease is proposed to be related with anemia. In line to this notion, low levels of hemoglobin and red blood cell have been reported in patients suffering from Alzheimer’s disease (AD), a chronic neurodegenerative disease caused by β-amyloid peptide (Aβ) accumulation. Therefore, we would like to probe the neuroprotective functions of this ancient herbal formula in vitro. Method The neuroprotective effects of DBT in the Aβ-induced cell death were detected in cultured cortical neurons by multiple techniques, i.e. confocal and western blot. Results In the cultures, application of DBT reduced Aβ-induced apoptosis rate in a dose-dependent manner. In Aβ-treated cortical neurons, the expression ratio of Bcl2 to Bax was altered by DBT. In parallel, application of DBT markedly suppressed the Aβ-induced expressions of apoptotic markers, i.e. cleaved-caspase 3/9 and PARP. Conclusion Taken these results, DBT shows promising protective effects against Aβ-induced stress or insult in cultured neurons.

The fruits of Ziziphus jujuba, commonly known as jujube, red date or Chinese date, are taken as fresh or dried food, and as traditional medicine worldwide due to high nutritional and health values. Traditionally in China, jujube is considered as a medicinal fruit that is being used in treating blood deficiency. In this review, the beneficial effects of jujubes on the hematopoietic functions are summarized and discussed. As illustrated in cell and animal models, the application of jujube extract possessed beneficial effects, including regulation of erythropoiesis via activation of hypoxia inducible factor-induced erythropoietin, potential capacity in recycling heme iron during erythrophagocytosis and bi-directional regulation of immune response. Thus, the blood-nourishing function of jujube is being proposed here. Flavonoid, polysaccharide and triterpenoid within jujube could serve as the potential active ingredients accounting for the aforementioned health benefits. Taken together, these findings provide several lines of evidence for further development of jujube as supplementary products for prevention and/or treatment of anemia.

Abstract Background A Chinese herbal formula, namely Jian-Pi-Yi-Shen (JPYS), has been clinically prescribed for patients with chronic kidney disease associated-anemia, and which can improve the patient’s immunological system. However, the mechanisms of JPYS involved in anemia and immune response have not been investigated. To study the role of JPYS in regulating hematopoietic and immunological functions, we investigated its activities on the expressions of erythropoietin and pro-inflammatory cytokines in cultured cells. Methods The standardized herbal extracts of JPYS (0–30 μg/ml) were applied onto cultured cells for 24–48 h. Total RNA was collected from the treated cells and subjected to real-time quantitative PCR analysis. Cultured HEK293T cells, transfected with a construct composed of hypoxia response element tagged with a luciferase gene, i.e. pHRE-Luc, were treated with JPYS extracts (1–30 μg/ml) for 24 h. The cell lysates were subjected to luciferase assay. Results The treatment with JPYS extract onto cultured HEK293T cells induced erythropoietin expression in a dose-dependent manner, having the highest response by ~ 50% of increase. In parallel, application of JPYS extract for 24 h stimulated expressions of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in cultured RAW 264.7 macrophages. In contrast, the pretreatment with JPYS extract suppressed expressions of IL-1β, IL-6, and TNF-α in lipopolysaccharide-induced macrophages. Conclusions These results confirmed the hematopoietic function of JPYS in regulating erythropoietin expression, as well as the bidirectional immune-modulatory roles of JPYS by regulating the expression of pro-inflammatory cytokines in cultures.

Stephaniae tetrandrae radix (STR) is a commonly used traditional Chinese medicine in alleviating edema by inducing diuresis. In the clinic, STR extracts or its components are widely used in the treatment of edema, dysuria, and rheumatism for the regulation of water metabolism. Furthermore, STR has been used in treating emotional problems for years by combining with other Chinese herbs. However, the material basis and mechanism of STR on the nervous system have not been revealed. Here, the main components of STR extracts with different extracting solvents were identified, including three major alkaloids, i.e., cyclanoline, fangchinoline, and tetrandrine. The cholinesterase inhibitory activity of STR extracts and its alkaloids was determined using the Ellman assay. Both cyclanoline and fangchinoline showed acetylcholinesterase (AChE) inhibitory activity, demonstrating noncompetitive enzyme inhibition. In contrast, tetrandrine did not show enzymatic inhibition. The synergism of STR alkaloids with huperzine A or donepezil was calculated by the median-effect principle. The drug combination of fangchinoline–huperzine A or donepezil synergistically inhibited AChE, having a combination index (CI) < 1 at Fa = 0.5. Furthermore, the molecular docking results showed that fangchinoline bound with AChE residues in the peripheral anionic site, and cyclanoline bound with AChE residues in the peripheral anionic site, anionic site, and catalytic site. In parallel, cyclanoline bound with butyrylcholinesterase (BChE) residues in the anionic site, catalytic site, and aromatic site. The results support that fangchinoline and cyclanoline, alkaloids derived from STR, could account for the anti-AChE function of STR. Thus, STR extract or its alkaloids may potentially be developed as a therapeutic strategy for Alzheimer’s patients.

A reliable ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS) method for the fast simultaneous determination of 13 nucleosides and nucleobases in Cordyceps sinensis (C. sinensis) with 2-chloroadenosine as internal standard was developed and validated. Samples were ultrasonically extracted in an ice bath thrice, and the optimum analyte separation was performed on an ACQUITY UPLCTM HSS C18 column (100 mm × 2.1 mm, 1.8 μm) with gradient elution. All targeted analytes were separated in 5.5 min. Furthermore, all calibration curves showed good linear regression (r > 0.9970) within the test ranges, and the limits of quantitation and detection of the 13 analytes were less than 150 and 75 ng/mL, respectively. The relative standard deviations (RSDs) of intra- and inter-day precisions were

Cordyceps sinensis is an endoparasitic fungus widely used as a tonic and medicinal food in the practice of traditional Chinese medicine (TCM). In historical usage, Cordyceps specifically is referring to the species of C. sinensis. However, a number of closely related species are named themselves as Cordyceps, and they are sold commonly as C. sinensis. The substitutes and adulterants of C. sinensis are often introduced either intentionally or accidentally in the herbal market, which seriously affects the therapeutic effects or even leads to life-threatening poisoning. Here, we aim to identify Cordyceps by DNA sequencing technology. Two different DNA-based approaches were compared. The internal transcribed spacer (ITS) sequences and the random amplified polymorphic DNA (RAPD)-sequence characterized amplified region (SCAR) were developed here to authenticate different species of Cordyceps. Both approaches generally enabled discrimination of C. sinensis from others. The application of the two methods, supporting each other, increases the security of identification. For better reproducibility and faster analysis, the SCAR markers derived from the RAPD results provide a new method for quick authentication of Cordyceps.

Chemo-resistance is an obstacle in therapy of lung cancer. Alternative therapy of using herbal medicine has been proposed to resolve this obstacle. Yu Ping Feng San (YPFS), a common Chinese herbal medicinal mixture, has been reported to show anti-drug resistance on cisplatin (DDP), a common lung cancer drug. To optimize the anti-cancer function of YPFS, different Chinese herbal extracts having known function to overcome lung cancer were screened in combining with YPFS, as to increase the efficacy of DDP in drug resistance lung cancer cell, A549/DDP. Amongst these herbal extracts, Ginkgo Folium exhibited the most promoting sensitized effect. This revised herbal formula, named as YPFS+GF, promoted the DDP-induced toxicity by over 2-fold as compared to that of YPFS alone; this potentiation was confirmed by inducing cell apoptosis. The anti-drug resistance of YPFS, triggered by an increase of intracellular concentration of DDP, was accompanied by an increased expression and activity of WT1, which consequently decreased the transcript level of MVP. In addition, the MVP-mediated downstream effector mTOR2/AKT was disrupted after application of YPFS+GF in DDP-treated A549/DDP cell: this disruption was characterized by the decline of mTORC2 components, e.g., Rictor, p-mTOR, as well as the phosphorylation level of its downstream protein AKT. The disruption on mTORC2/AKT could be reversed by mTORC2 inducer insulin and promoted by mTORC2 inhibitor PP242. Thus, the anti-drug resistance of YPFS+GF in DDP-treated lung cancer cells might be mediated by the down regulation of WT1/MVP axis, as well as the downstream anti-apoptotic pathway of mTORC2/AKT signaling. Herbal medicine is one of the main adjuvant therapies in non-small cell lung cancer, and this novel herbal formula supports the prescription of traditional Chinese medicine in cancer treatment.

Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction commonly used to mitigate menopausal osteoporosis, contains two herbs: Astragali Radix (AR) and Angelicae Sinensis Radix (ASR). The exact efficacy of individual chemical(s) within DBT, or in any herbal mixture, is hard to be revealed. Calycosin and ferulic acid have been reported to be the predominant chemicals found within DBT, and its roles in regulating osteoblastic differentiation have been proposed here. To probe the roles of calycosin and ferulic acid, these chemicals were specifically depleted from the DBT extracts. Here, calycosin-depleted DBT (DBTΔcal) and ferulic acid-depleted DBT (DBTΔfa), generated by semi-preparative HPLC, were coupled with RNA-seq and metabolomics analyses to reveal the synergistic functions of individual chemicals within a complex herbal mixture. The expressions of osteogenic differentiation markers were significantly increased under the treatments of DBT and DBTΔfa. The DBT-induced genes were markedly reduced in the absent of calycosin, i.e., DBTΔcal. In cultured osteoblasts, the DBT-activated Wnt/β-catenin and MAPK/Erk and signaling pathways were greatly affected when calycosin was depleted. By metabolomics analysis in DBT-treated osteoblasts, the profile of metabolites triggered by DBTΔcal showed distinction to that of DBT and/or DBTΔfa. Thus, our findings indicated that calycosin, rather than ferulic acid, could be an indispensable chemical in DBT to orchestrate multi-components of DBT in achieving maximal osteogenic properties.

Genistein, 4′,5,7-trihydroxyisoflavone, is a major isoflavone in soybean, which is known as phytestrogen having known benefit to brain functions. Being a common phytestrogen, the possible role of genistein in the brain protection needs to be further explored. In cultured PC12 cells, application of genistein significantly induced the expression of neurofilaments (NFs), markers for neuronal differentiation. In parallel, the expression of tetrameric form of proline-rich membrane anchor (PRiMA)-linked acetyl-cholinesterase (G4 AChE), a key enzyme to hydrolyze acetylcholine in cholinergic synapses, was induced in a dose-dependent manner: this induction included the associated protein PRiMA. The genistein-induced AChE expression was fully blocked by the pre-treatment of H89 (an inhibitor of protein kinase A, PKA) and G15 (a selective G protein-coupled receptor 30 (GPR30) antagonist), which suggested a direct involvement of a membrane-bound estrogen receptor (ER), named as GPR30 in the cultures. In parallel, the estrogen-induced activation of GPR30 induced AChE expression in a dose-dependent manner. The genistein/estrogen-induced AChE expression was triggered by a cyclic AMP responding element (CRE) located on the ACHE gene promoter. The binding of this CRE site by cAMP response element-binding protein (CREB) induced ACHE gene transcription. In parallel, increased expression levels of miR132 and miR212 were found when cultured PC12 cells were treated with genistein or G1. Thus, a balance between production and destruction of AChE by the activation of GPR30 was reported here. We have shown for the first time that the activation of GPR30 could be one way for estrogen or flavonoids, possessing estrogenic properties, to enhance cholinergic functions in the brain, which could be a good candidate for possible treatment of neurodegenerative diseases.

Angelica Radix, the roots of the genus Angelica, has been used for more than 2,000 years as a traditional medicine in Eastern Asia. The Chinese Pharmacopoeia records more than 100 herbal formulae containing Angelica roots. There are two common sources of Angelica roots, Angelica sinensis from China and A. gigas from Korea. The two species of Angelica roots differ in their chemical compositions, pharmacological properties and clinical efficacy. 1H-NMR metabolic profiling has recently emerged as a promising quality control method for food and herbal chemistry. We explored the use of 1H-NMR metabolic profiling for the quality control of Angelica Radix. Unlike previous work, we performed the metabolic profiling on hot water extracts, so as to mimic the clinically relevant preparation method. Unsupervised principle component analyses of both the full spectral profile and a selection of targeted molecules revealed a clear differentiation of three types of Angelica roots. In addition, the levels of 13 common metabolites were measured. Statistically significant differences in the levels of glucose, fructose and threonine were found between different sources of Angelica. Ferulic acid, a marker commonly used to evaluate Angelica root, was detected in our samples, but the difference in ferulic acid levels between the samples was not statistically significant. Overall, we successfully applied 1H-NMR metabolic profiling with water extraction to discriminate all three sources of Angelica roots, and obtained quantitative information of many common metabolites.

Bulbus Fritillariae is the most commonly used antitussive herb in China. Eleven species of Fritillaria are recorded as Bulbus Fritillariae in the Chinese Pharmacopoeia. Bulbus Fritillariae Cirrhosae is a group of six Fritillaria species with higher efficiency and lower toxicity derived mainly from wild sources. Because of their higher market price, five other Fritillaria species are often sold deceptively as Bulbus Fritillariae Cirrhosae in the herbal market. To ensure the efficacy and safety of medicinal herbs, the authentication of botanical resources is the first step in quality control. Here, a DNA based identification method was developed to authenticate the commercial sources of Bulbus Fritillariae Cirrhosae. A putative DNA marker (0.65 kb) specific for Bulbus Fritillariae Cirrhosae was identified using the Random Amplified Polymorphic DNA (RAPD) technique. A DNA marker representing a Sequence Characterized Amplified Region (SCAR) was developed from a RAPD amplicon. The SCAR marker was successfully applied to differentiate Bulbus Fritillariae Cirrhosae from different species of Fritillaria. Additionally, the SCAR marker was also useful in identifying the commercial samples of Bulbus Fritillariae Cirrhosae. Our results indicated that the RAPD-SCAR method was rapid, accurate and applicable in identifying Bulbus Fritillariae Cirrhosae at the DNA level.

Gut microbiota play an important role in metabolism of intake saponins, and parallelly, the polysaccharides deriving from herbal products possess effects on gut microbiota. Ophiopogonis Radix is a common Chinese herb that is popularly used as functional food in China. Polysaccharide and steroidal saponin, e.g., ophiopogonin, mainly ophiopogonin D (Oph-D) and ophiopogonin D’ (Oph-D’), are the major constituents in this herb. In order to reveal the role of gut microbiota in metabolizing ophiopogonin, an in vitro metabolism of Oph-D and Oph-D’ by human gut microbiota, in combination with or without Ophiopogon polysaccharide, was conducted. A sensitive and reliable UPLC-MS/MS method was developed to simultaneously quantify Oph-D, Oph-D’ and their final metabolites, i.e., ruscogenin and diosgenin in the broth of microbiota. An elimination of Oph-D and Oph-D’ was revealed in a time-dependent manner, as well as the recognition of a parallel increase of ruscogenin and diosgenin. Ophiopogon polysaccharide was shown to stimulate the gut microbiota-induced metabolism of ophiopogonins. This promoting effect was further verified by increased activities of β-D-glucosidase, β-D-xylosidase, α-L-rhamnosidase and β-D-fucosidase in the broth. This study can be extended to investigate the metabolism of steroidal saponins by gut microbiota when combined with other herbal products, especially those herbs enriched with polysaccharides.

Astragali Radix (AR), a Chinese materia medica (CMM) known as Huangqi, is an important medicine prescribed in herbal composite formulae (Fufang) by Traditional Chinese medicine (TCM) practitioners for thousands of years. According to the literature, AR is suggested for patients suffering from “Qi”- and “Blood”-deficiencies, and its clinical effects are reported to be related to anti-cancer cell proliferation, anti-oxidation, relief of complications in cardiovascular diseases, etc. The underlying cell signaling pathways involved in the regulation of these various diseases are presented here to support the mechanisms of action of AR. There are two botanical sources recorded in China Pharmacopoeia (CP, 2015): Astragalus membranaceus (Fisch.) Bge. Var. mongohlicus, (Bge.) Hsiao, and Astragalus membranaceus (Fisch.) Bge. (Fam. Leguminosae), whose extracts of dried roots are processed via homogenization-assisted negative pressure cavitation extraction. Geographic factors and extraction methods have impacts on the pharmaceutical and chemical profiles of AR. Therefore, the levels of the major bioactive constituents of AR, including polysaccharides, saponins, and flavonoids, may not be consistent in different batches of extract, and the pharmaceutical efficacy of these bioactive ingredients may vary depending on the source. Therefore, the present review mainly focuses on the consistency of the available sources of AR and extracts and on the investigation of the biological functions and mechanisms of action of AR and of its major bioactive constituents. Furthermore, it will also include a discussion of the most popular AR composite formulae to further elucidate their chemical and biological profiles and understand the pharmaceutical value of AR.

The plant Leucaena leucocephala was exposed to four jasmonate elicitors, i.e., jasmonic acid (JA), methyl jasmonic acid (MeJA), jasmonoyl-l-isoleucine (JA-Ile) and 6-ethyl indanoyl glycine conjugate (2-[(6-ethyl-1-oxo-indane-4-carbonyl)-amino]-acetic acid methyl ester) (CGM). The treatment was to mimic the herbivores and wounding stresses. By using NMR spectroscopy along with chemometric analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), the changes of metabolites in the leaves of L. leucocephala were determined under the stress as induced by the four elicitors. The challenge of JA-Ile caused an accumulation of lactic acid (6), β-glucose (10), alanine (12), threonine (13), steroids (18), 3,4-dihydroxypyridine (19) and an unidentified compound 20. The chemometric analysis of the PCA and PLS-DA models indicated that the alternation of metabolites triggered by JA, MeJA, and CGM treatments were very minimum. In contrast, the treatment by JA-Ile could induce the most significant metabolic changes in the leaves. Moreover, there was very minimal new metabolite being detected in responding to the jasmonate-induced stresses. The results showed some metabolite concentrations changed after application of the elicitors, which may be related to a high level of tolerance to stress conditions as well as the strong ecological suitability of L. leucocephala.

Angelica Radix, the roots of the genus Angelica, has been used for more than 2,000 years as a traditional medicine in Eastern Asia. The Chinese Pharmacopoeia records more than 100 herbal formulae containing Angelica roots. There are two common sources of Angelica roots, Angelica sinensis from China and A. gigas from Korea. The two species of Angelica roots differ in their chemical compositions, pharmacological properties and clinical efficacy. 1H-NMR metabolic profiling has recently emerged as a promising quality control method for food and herbal chemistry. We explored the use of 1H-NMR metabolic profiling for the quality control of Angelica Radix. Unlike previous work, we performed the metabolic profiling on hot water extracts, so as to mimic the clinically relevant preparation method. Unsupervised principle component analyses of both the full spectral profile and a selection of targeted molecules revealed a clear differentiation of three types of Angelica roots. In addition, the levels of 13 common metabolites were measured. Statistically significant differences in the levels of glucose, fructose and threonine were found between different sources of Angelica. Ferulic acid, a marker commonly used to evaluate Angelica root, was detected in our samples, but the difference in ferulic acid levels between the samples was not statistically significant. Overall, we successfully applied 1H-NMR metabolic profiling with water extraction to discriminate all three sources of Angelica roots, and obtained quantitative information of many common metabolites. [ABSTRACT FROM AUTHOR]

Neurotrophic factors are playing vital roles in survival, growth, and function of neurons. Regulation of neurotrophic factors in the brain has been considered as one of the targets in developing drug or therapy against neuronal disorders. Flavonoids, a family of multifunctional natural compounds, are well known for their neuronal beneficial effects. Here, the effects of flavonoids on regulating neurotrophic factors were analyzed in cultured rat astrocytes. Astrocyte is a major secreting source of neurotrophic factors in the brain. Thirty-three flavonoids were screened in the cultures, and calycosin, isorhamnetin, luteolin, and genistein were identified to be highly active in inducing the synthesis and secretion of neurotrophic factors, including nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF). The inductions were in time- and dose-dependent manners. In cultured astrocytes, the phosphorylation of estrogen receptor was triggered by application of flavonoids. The phosphorylation was blocked by an inhibitor of estrogen receptor, which in parallel reduced the flavonoid-induced expression of neurotrophic factors. The results proposed the role of flavonoids in protecting brain diseases, and therefore these flavonoids could be developed for health food supplement for patients suffering from neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Identifying potent drug combination from a herbal mixture is usually quite challenging, due to a large number of possible trials. Using an engineering approach of the feedback system control (FSC) scheme, we identified the potential best combinations of four flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-D-glucoside deriving from Astragali Radix (AR; Huangqi), which provided the best biological action at minimal doses. Out of more than one thousand possible combinations, only tens of trials were required to optimize the flavonoid combinations that stimulated a maximal transcriptional activity of hypoxia response element (HRE), a critical regulator for erythropoietin (EPO) transcription, in cultured human embryonic kidney fibroblast (HEK293T). By using FSC scheme, 90% of the work and time can be saved, and the optimized flavonoid combinations increased the HRE mediated transcriptional activity by ~3-fold as compared with individual flavonoid, while the amount of flavonoids was reduced by ~10-fold. Our study suggests that the optimized combination of flavonoids may have strong effect in activating the regulatory element of erythropoietin at very low dosage, which may be used as new source of natural hematopoietic agent. The present work also indicates that the FSC scheme is able to serve as an efficient and model-free approach to optimize the drug combination of different ingredients within a herbal decoction. [ABSTRACT FROM AUTHOR]

Roots of Angelica sinensis (Danggui) have been used in promoting blood circulation as herbal medicine for over 2000 years in China. Another species of Angelica roots ailed A. gigas is being used in Korea. To reveal the efficiency of different Angelica roots, the chemical and biological properties of Angelica roots from different cultivated regions were compared. Roots of A. sinensis contained higher levels of ferulic acid, Z-ligustilide, and senkyunolide A, while high amounts of butylphthalide and Z-butylenephthalide were found in A. gigas roots. The extracts deriving from A. gigas roots showed better effects in osteogenic and estrogenic properties than that of A. sinensis from China. However, this difference was markedly reduced when the Angelica roots were being prepared in a Chinese herbal decoction together with Astragali Radix as Danggui Buxue Tang. In contrast, the herbal decoction prepared from A. sinensis roots showed better responses in cell cultures. In addition, the extracts of A. gigas roots showed strong cell toxicity both as single herb and as Danggui Buxue Tang. This result revealed the distinct properties of Angelica roots from China and Korea suggesting the specific usage of herb in preparing a unique herbal decoction. [ABSTRACT FROM AUTHOR]