Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model.

Berberine (BBR), a major active constituent of Rhizoma coptidis, was reported to exert beneficial effects on intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). However, the bioavailability of BBR is extremely low, and its metabolites were perceived to contribute to its prominent pharmacological activities. Oxyberberine (OBB) is a gut metabolite of BBR, which has been reported to have a superior anti-inflammatory effect in experimental colitis. However, its anti-inflammatory effects against 5-FU-induced IM mice have not yet been investigated. Hence, the purpose of this study was to reveal the protective effects of OBB on IM induced by 5-FU and investigate its potential underlying mechanism. The IM mice model was induced by receiving 5-FU (60 mg/kg, i.p.) for five days. Meanwhile, BBR (50 mg/kg) and OBB (12.5, 25, and 50 mg/kg) were given prior to 30 min intraperitoneal injection of 5-FU for seven days. Results indicated that OBB ameliorated body weight loss, anorexia, diarrhea, and histopathological damage in 5-FU-induced IM mice. After OBB administration, the amounts of MDA, SOD, and GSH altered by IM were remarkably restored. OBB was also observed to dramatically decrease the levels of TNF-α, IL-8, IL-6, COX-2, and iNOS and promote the release of IL-10. Besides, OBB distinctly upregulated the mRNA expressions of PCNA, ZO-1, occludin, and mucin-1, which could improve intestinal homeostasis in IM mice. OBB also blocked the activation of the upstream TLR4/MyD88 signaling pathway, and then it inhibited the phosphorylation of the NF-κB and MAPK pathways. Importantly, compared with BBR, OBB displayed a superior therapeutic effect to BBR in alleviating 5-FU-induced IM mice. These results indicated that OBB has considerable potential to become a novel candidate drug against IM.

Ameliorative effect of supercritical fluid extract of Chrysanthemum indicum Linnén against D-galactose induced brain and liver injury in senescent mice via suppression of oxidative stress, inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum Linne (C. indicum), a healthy food and folk medicine in China for thousands of years, has been reported to exert heat-clearing and detoxifying effects and extensively applied to treat various symptoms such as inflammation diseases, hepatitis and headache. AIM OF THIS STUDY: The purpose of the present study was to investigate the protective effect of the supercritical carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) on D-galactose-induced brain and liver damage during aging process and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with CISCFE (100, 150 and 300 mg/kg) after injection with D-galactose. 24 h after the last administration, the blood samples, whole brain and liver tissues were collected for biochemical analysis, histological examination and western blot analysis. The body weight, spleen and thymus indexes, alanine transaminase (ALT), aspartate transaminase (AST), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in brain and liver, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and necrosis factor-α (TNF-α) were detected. Besides, the expressions of Bax, Bcl-2 and cleaved caspase-3 were determined by western blot assay. RESULTS: The results indicated that CISCFE effectively increased the suppressed body weight, attenuated the decline of thymus and spleen indexes, and reduced the elevated levels of ALT and AST induced by D-gal. Furthermore, CISCFE might notably alleviate D-gal-induced abnormal alterations in structure and function of brain and liver dose-dependently via renewing normal antioxidant enzymes activities (SOD, CAT, GSH-Px), reducing MDA accumulation, decreasing inflammatory cytokines productions (IL-1ß, IL-6, TNF-α), as well as attenuating the increase of Bax/Bcl-2 ratio and cleaved caspase-3 activation in the liver and brain. CONCLUSIONS: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and liver diseases.

Patchoulene Epoxide Isolated from Patchouli Oil Suppresses Acute Inflammation through Inhibition of NF-κB and Downregulation of COX-2/iNOS.

According to the GC-MS analysis, compositional variation was observed between samples of patchouli oil, of which an unknown compound identified as patchoulene epoxide (PAO) was found only in the long-stored oil, whose biological activity still remains unknown. Therefore, the present study aimed to evaluate the potential anti-inflammatory activity with three in vivo inflammatory models: xylene-induced ear edema, acetic acid-induced vascular permeability, and carrageenan-induced paw edema. Further investigation into its underlying mechanism on carrageenan-induced paw edema was conducted. Results demonstrated that PAO significantly inhibited the ear edema induced by xylene, lowered vascular permeability induced by acetic acid and decreased the paw edema induced by carrageenan. Moreover, PAO markedly decreased levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO), but increased levels of interleukin-4 (IL-4) and interleukin-10 (IL-10). PAO was also shown to significantly downregulate the protein and mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS). Western blot analysis revealed that PAO remarkably inhibited p50 and p65 translocation from the cytosol to the nucleus by suppressing IKKß and IκBα phosphorylation. In conclusion, PAO exhibited potent anti-inflammatory activity probably by suppressing the activation of iNOS, COX-2 and NF-κB signaling pathways.

Different effects of (+)­borneol and (­)­borneol on the pharmacokinetics of osthole in rats following oral administration.

Osthole is the primary active component of a number of herbal plants such as the Cnidium monnieri fruit. In traditional Chinese herb medicine, osthole is commonly used in combination with borneol to obtain improved pharmacological effects. The aim of the present study was to investigate the effect of borneol enantiomers on the pharmacokinetics of osthole. An appropriate high­performance liquid chromatography (HPLC) method was applied to determine the concentrations of osthole in plasma. Following oral administration of osthole alone or combined with borneol in rats, blood samples were collected and analyzed by HPLC. The results demonstrated that there were statistically significant differences in the pharmacokinetic parameters of osthole between osthole administration alone and co­administration with borneol. When combined with synthetic borneol, the AUC0­t, AUC0­∞ and Cmax of osthole increased by 48.153, 104.708 and 92.630%, respectively, while the CL/F decreased by 51.251%. When combined with (+)­borneol, the AUC0­t, AUC0­∞ and Cmax of osthole were increased by 61.561, 78.167, and 51.769%, respectively, while the CL/F decreased by 44.174% (P<0.01). In addition, when combined with (­)­borneol, the AUC0­t, AUC0­∞ and Cmax of osthole increased by 115.856, 167.786 and 271.289%, respectively, while the CL/F decreased by 60.686% (P<0.01). These results indicated that borneol may enhance gastrointestinal absorption and inhibit the metabolism of osthole. In addition, the promotional effect of (­)­borneol on the pharmacokinetic parameters of osthole was greater than that of (+)­borneol.

Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF-κB Pathway.

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responses via decreasing the expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPS via inhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting.

Protective Effect of SFE-CO2 of Ligusticum chuanxiong Hort Against d-Galactose-Induced Injury in the Mouse Liver and Kidney.

This study was designed to explore how supercritical fluid CO2 extract of Ligusticum chuanxiong Hort (CX) protects mouse liver and kidney from d-galactose-induced injury. The antioxidant capacity of CX was confirmed both in vitro and in vivo. The d-galactose-induced malondialdehyde increase was attenuated by CX, as well as the increase in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine level. In addition, the activities of antioxidant enzymes were markedly renewed, and the gene expressions of these enzymes were upregulated in CX groups. The results of histological analysis suggested that CX could effectively attenuate the d-galactose-induced structure damage. Furthermore, results of Western blotting analysis showed that CX significantly inhibited the upregulation of nuclear factor protein expression caused by d-galactose. In conclusion, CX could attenuate the liver and kidney injury in d-galactose-treated mice, and the mechanism might be associated with attenuating oxidative stress and inflammatory response.

Photo-protective activity of pogostone against UV-induced skin premature aging in mice.

Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.

Protective Effect of Super-Critical Carbon Dioxide Fluid Extract from Flowers and Buds of Chrysanthemum indicum Linnén Against Ultraviolet-Induced Photo-Aging in Mice.

It is known that solar ultraviolet (UV) radiation to human skin causes photo-aging, including increases in skin thickness and wrinkle formation and reduction in skin elasticity. UV radiation induces damage to skin mainly by superfluous reactive oxygen species and chronic low-grade inflammation, which eventually up-regulate the expression of matrix metalloproteinases (MMPs). In this study, the super-critical carbon dioxide extract from flowers and buds of Chrysanthemum indicum Linnén (CISCFE), which has been reported to possess free radical scavenging and anti-inflammatory properties, was investigated for its photo-protective effect by topical application on the skin of mice. Moreover, CISCFE effectively suppressed the UV-induced increase in skin thickness and wrinkle grading in a dose-dependent manner, which was correlated with the inhibition of loss of collagen fiber content and epidermal thickening. Furthermore, we observed that CISCFE could obviously decrease UV-induced skin inflammation by inhibiting the production of inflammatory cytokines (interleukin-1ß [IL-1ß, IL-6, IL-10, tumor necrosis factor-α), alleviate the abnormal changes of anti-oxidative indicators (superoxide dismutase, catalase, and glutathione peroxidase), and down-regulate the levels of MMP-1 and MMP-3. The results indicated that CISCFE was a novel photo-protective agent from natural resources against UV irradiation.

The sulfur-fumigation reduces chemical composition and biological properties of Angelicae Sinensis Radix.

Angelica Sinensis Radix (roots of Angelica sinensis; ASR) is a popular herbal supplement in China for promoting blood circulation. Today, sulfur-fumigation is commonly used to treat ASR as a means of pest control; however, the studies of sulfur-fumigation on the safety and efficacy of ASR are very limited. Here, we elucidated the destructive roles of sulfur-fumigation on ASR by chemical and biological assessments. After sulfur-fumigation, the chemicals in ASR were significantly lost. The biological activities of anti-platelet aggregation, induction of NO production and estrogenic properties were compared between the water extracts of non-fumigated and sulfur-fumigated ASR. In all cases, the sulfur-fumigation significantly reduced the biological properties of ASR. In addition, application of water extract deriving from sulfur-fumigated ASR showed toxicity to cultured MCF-7 cells. In order to ensure the safety and to achieve the best therapeutic effect, it is recommended that sulfur-fumigation is an unacceptable approach for processing herbal materials.

White pepper and piperine have different effects on pharmacokinetics of puerarin in rats.

This study attempted to explore the effects of white pepper and its major component piperine on puerarin administered to rats. Pharmacokinetic parameters of puerarin in rats were determined by oral administration (400 mg/kg) or intravenous injection (40 mg/kg) of puerarin, pretreated with or without white pepper and piperine given orally. Compared to the control group given oral puerarin only, the combined use of piperine (10 or 20 mg/kg) increased the C max of puerarin by 1.30-fold or 1.64-fold and the AUC0-∞ by 133% or 157%, respectively. In contrast, coadministration of white pepper (125 or 250 mg/kg) decreased oral absorption of puerarin to 83% or 74%, respectively. On the other hand, pretreatment with piperine orally did not alter the intravenous pharmacokinetics of puerarin, while the AUC of puerarin after intravenous administration was increased by pretreatment with white pepper. The results indicate that pretreatment with piperine or pepper exerts different effects on pharmacokinetics of puerarin administrated via intragastric and intravenous routes. Therefore, it is suggested that the combined application of piperine or white pepper with puerarin should be carefully monitored for potential diet-drug interactions.

Identification of Angelica oil as a suppressor for the biological properties of Danggui Buxue Tang: a Chinese herbal decoction composes of Astragali Radix and Angelica Sinensis Radix.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Tang (DBT), a Chinese herbal decoction commonly used in treating women׳s ailments, contains two herbs: Angelica Sinensis Radix (ASR) and Astragali Radix (AR). Traditionally, ASR had to be pre-treated with yellow wine before the herbal preparation, which reduced the amount of volatile oil in water extract of ASR and DBT, and meanwhile the volatile oil-reduced DBT processed better bioactivities in cell cultures. The present study aimed to investigate the effect of volatile oil from ASR (Angelica oil) on the solubility of AR-derived ingredients and the biological properties of DBT. MATERIALS AND METHODS: To standardize Angelica oil, four marker chemicals in ASR were determined by GC-QQQ-MS/MS. Subsequently, fifteen gram of AR was boiled with different amounts of Angelica oil. The amounts of astragaloside IV, calycosin, formononetin, total polysaccharides, total saponins and total flavonoids, all derived from AR, were extracted and determined by HPLC-UV/ELSD. To reveal the effect of Angelica oil on DBT functions, several cell assays related to the traditional functions of DBT were selected, including anti-platelet aggregation, induction of NO production, hematopoetic, estrogenic and osteogenic properties. RESULTS: The inclusion of Angelica oil in AR during preparation significantly decreased the amount of AR-derived astragaloside IV, calycosin, formononetin, total saponins and total flavonoids in the final water extract. In parallel, an inclusion of Angelica oil caused a decrease of DBT׳s estrogenic and hematopoetic activities in cultured cells. Moreover, the Angelica oil decreased DBT-induced cell proliferation of cultured MG-63 and endothelial cells. CONCLUSIONS: The results indicated that Angelica oil was a negative regulator for DBT chemically and biologically, which supported the traditional practice of preparing DBT by using the wine-treated ASR.

Protection Effect of Zhen-Wu-Tang on Adriamycin-Induced Nephrotic Syndrome via Inhibiting Oxidative Lesions and Inflammation Damage.

Zhen-wu-tang (ZWT), a well-known formula in China, is widely used to treat chronic kidney diseases. However, very little information on ZWT's mechanism of action is currently available. In this study, we investigated the possible protective role and underlying mechanism of ZWT on nephrotic syndrome (NS) induced by Adriamycin (intravenous injection, 6.0 mg/kg) in rats using biochemical and histopathological approaches. ZWT decreased urine protein excretion and the serum levels of total cholesterol, triglycerides, blood urea nitrogen, and creatinine significantly in diseased rats. A decrease in plasma levels of total protein and albumin was also recorded in nephropathic rats. Pathological results show an improved pathological state and recovering glomerular structure in ZWT treatment groups. ZWT decreased renal IL-8 level but increased renal IL-4 level. In addition, rats subjected to ZWT exhibited less IgG deposition in glomerulus compared with model group. RT-PCR results showed that ZWT decreased the mRNA expression of NF- κ B p65 and increased the mRNA expression of I κ B. Furthermore, ZWT reduced the level of MDA and increased SOD activity. These results demonstrated that ZWT ameliorated Adriamycin-induced NS in rats possibly by inhibiting Adriamycin-induced inflammation damage, enhancing body's antioxidant capacity, thereby protecting glomerulus from injury.

Hydrolysis of Glycosidic Flavonoids during the Preparation of Danggui Buxue Tang: An Outcome of Moderate Boiling of Chinese Herbal Mixture.

Chemical change during boiling of herbal mixture is a puzzle. By using Danggui Buxue Tang (DBT), a herbal decoction that contains Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), we developed a model in analyzing the hydrolysis of flavonoid glycosides during the boiling of herbal mixture in water. A proper preparation of DBT is of great benefit to the complete extraction of bioactive ingredients. Boiling of DBT in water increased the solubility of AR-derived astragaloside IV, calycosin, formononetin, calycosin-7-O- ß -D-glucoside, and ononin in a time- and temperature-dependent manner: the amounts of these chemicals reached a peak at 2 h. The glycosidic resides of AR, calycosin-7-O- ß -D-glucoside, and ononin could be hydrolyzed during the moderate boiling process to form calycosin and formononetin, respectively. The hydrolysis efficiency was strongly affected by pH, temperature, and amount of herbs. Interestingly, the preheated herbs were not able to show this hydrolytic activity. The current results supported the rationality of ancient preparation of DBT in boiling water by moderate heat.

Prevention of UV radiation-induced cutaneous photoaging in mice by topical administration of patchouli oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin has been widely used in traditional Chinese medicine for the treatment of many diseases, including skin disorders. In the skin beauty and care prescriptions, Pogostemon cablin is one of the top ten frequently used traditional Chinese medicines. AIM OF THE STUDY: The present study was aimed to investigate the protective effects of the essential oil of Pogostemon cablin (patchouli oil, PO) against UV-induced skin photoaging in mice. MATERIALS AND METHODS: To ensure the quality of PO, the chemical compositions of PO were identified, and the content of its chemical marker patchouli alcohol was determined, which was around 28.2% (g/g) in PO. During the experiment period, the dorsal depilated skin of mice was treated with PO for two hours prior to UV irradiation. Then the protective effects of PO on UV-induced skin photoaging were determined by macroscopic and histological evaluations, skin elastic test, collagen content determination and biochemical assays of malondiaidehyde (MDA) content, activities of anti-oxidative indicators including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). RESULTS: Compared to UV exposure groups, present results showed that topical administration of PO, especially at dose of 6mg/mouse and 9mg/mouse, significantly inhibited the increase in skin wrinkle formation, alleviated the reduction in skin elasticity and increased the collagen content by about 21.9% and 26.3%, respectively. We also found that application of 6-9mg/mouse PO could not only decrease the epidermal thickness by about 32.6%, but also prevent the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, the content of MDA was decreased by almost 26.5% and activities of SOD, GSH-Px and CAT were significantly up-regulated after the treatment of PO. CONCLUSION: Results of present study revealed that PO was capable of maintaining skin structural integrity caused by UV irradiation and it was useful in preventing photoaging. These protective effects of PO were possibly due to its anti-oxidative property. Therefore, we suggested that PO should be viewed as a potential therapeutic agent for preventing photoaging.

Chemical changes of Angelicae Sinensis Radix and Chuanxiong Rhizoma by wine treatment: chemical profiling and marker selection by gas chromatography coupled with triple quadrupole mass spectrometry.

BACKGROUND: Angelicae Sinensis Radix (ASR) and Chuanxiong Rhizoma (CR) can be treated with wine to promote their biological functions in Chinese medicine. Both ASR and CR contain similar volatile chemicals that could be altered after wine treatment. This study aims to identify the differential chemical profiles and to select marker chemicals of ASR and CR before and after wine treatment. METHODS: Chemical analyses were carried out by gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS/MS) coupled with multivariate statistical analysis. Characterization of the compositions of essential oils was performed by automated matching to the MS library and comparisons of their mass spectra (NIST08 database). For ferulic acid, butylphthalide, Z-butylidenephthalide, senkyunolide A and Z-ligustilide, the mass spectrometer was operated in electron ionization mode, the selection reaction monitoring mode was used and an evaluation of the stability and sensitivity of the chromatographic system was performed for the tested extraction. RESULTS: Principal component analysis (PCA) simultaneously distinguished ASR and CR from different forms. Ferulic acid, Z-butylidenephthalide, Z-ligustilide, butylphthalide and senkyunolide A were screened by PCA loading plots and can be used as chemical markers for discrimination among different groups of samples. CONCLUSION: Different chemical profiles of ASR and CR after wine treatment could be identified by GC-QQQ-MS/MS. The five marker chemicals selected by PCA, namely ferulic acid, butylphthalide, Z-butylidenephthalide, senkyunolide A and Z-ligustilide, were sufficient to distinguish between the crude and corresponding wine-treated forms of ASR and CR.

Can Hedysari Radix replace Astragali Radix in Danggui Buxue Tang, a Chinese herbal decoction for woman aliment?

Astragali Radix (AR) has been used for over 2000 years in China for the enrichment of "Qi". Hedysari Radix (HR), a herb having similar chemical composition with AR, has been commonly used as a substitute of AR in herbal decoction. In order to evaluate the possible replacement of HR for AR in Chinese herbal decoction, systematic comparison of AR and HR was done by chemical and biological assessments. The water extract of AR contained higher levels of calycosin, calycosin-glucoside, ononin, astragaloside III and astragaloside IV, while higher amount of formononetin was found in the HR extract. The estrogenic, erythropoetic and osteogenic effects were compared between the water extracts of AR and HR, and in all cases AR extract showed higher biological activities. Danggui Buxue Tang (DBT) is a very common herbal decoction for woman aliment, and which contains AR and Angelica Sinensis Radix. Here, we generated two forms of DBT having either AR or HR as the major herbs. Chemically, AR-contained DBT showed higher amounts of various active chemicals, except formononetin that was higher in HR-contained DBT. In parallel, the estrogenic, osteogenic and erythropoetic effects of DBT containing AR showed better activities than that of DBT having HR. Thus, AR and HR showed distinct differences in terms of chemical and biological properties. In order to achieve the best therapeutical effect, as well as to guarantee the safety, AR is recommended here to be used for making DBT.

Chemical and biological assessment of Angelica herbal decoction: comparison of different preparations during historical applications.

The commonly used Angelica herbal decoction today is Danggui Buxue Tang (DBT), which is a dietary supplement in treating menopausal irregularity in women, i.e. to nourish "Qi" and to enrich "Blood". According to historical record, many herbal decoctions were also named DBT, but the most popular formulation of DBT was written in Jin dynasty (1247 AD) of China, which contained Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) with a weight ratio of 5:1. However, at least two other Angelica herbal decoctions recorded as DBT were prescribed in Song (1155 AD) and Qing dynasties (1687 AD). Although AR and ASR are still the major components in the DBT herbal decoctions, they are slightly varied in the herb composition. In order to reveal the efficiency of different Angelica herbal decoctions, the chemical and biological properties of three DBT herbal extracts were compared. Significantly, the highest amounts of AR-derived astragaloside III, astragaloside IV, calycosin and formononetin and ASR-derived ferulic acid were found in DBT described in 1247 AD: this preparation showed stronger activities in osteogenic, estrogenic and erythropoetic effects than the other two DBT. The current results supported the difference of three DBT in chemical and biological properties, which could be a result of different herbal combinations. For the first time, this study supports the popularity of DBT described in 1247 AD.

Salidroside stimulates the accumulation of HIF-1α protein resulted in the induction of EPO expression: a signaling via blocking the degradation pathway in kidney and liver cells.

Rhodiolae Crenulatae Radix et Rhizoma (Rhodiola), the root and rhizome of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba, has been used as a traditional Chinese medicine (TCM) to increase the body resistance to mountain sickness in preventing hypoxia; however, the functional ingredient responsible for this adaptogenic effect has not been revealed. Here, we have identified salidroside, a glycoside predominantly found in Rhodiola, is the chemical in providing such anti-hypoxia effect. Cultured human embryonic kidney fibroblast (HEK293T) and human hepatocellular carcinoma (HepG2) were used to reveal the mechanism of this hematopoietic function mediated by salidroside. The application of salidroside in cultures induced the expression of erythropoietin (EPO) mRNA from its transcription regulatory element hypoxia response element (HRE), located on EPO gene. The application of salidroside stimulated the accumulation of hypoxia-inducible factor-1α (HIF-1α) protein, but not HIF-2α protein: the salidroside-induced HIF-1α protein was via the reduction of HIF-1α degradation but not the mRNA induction. The increased HIF-1α could account for the activation of EPO gene. These results supported the notion that hematopoietic function of Rhodiola was triggered, at least partially, by salidroside.