Danggui-Shaoyao-San Research Articles

Mechanistic Study on the Antidepressant-Like Effect of Danggui-Shaoyao-San, a Chinese Herbal Formula

Danggui-Shaoyao-San (DSS), a famous Chinese herbal formula, has been widely used in the treatment of various diseases. Previous studies have shown that DSS produces antidepressant-like effect in rodents. This study aims to investigate the mechanism(s) underlying the antidepressant-like action of DDS. The results showed that DSS treatment significantly antagonized reserpine-induced ptosis in mice. In addition, DSS treatment significantly increased sucrose consumption in chronic unpredictable stress- (CUS-) treated mice. DSS treatment also markedly attenuated CUS-induced decreases in noradrenaline and dopamine concentrations in mouse brain. Furthermore, DSS treatment significantly reversed CUS-induced increase in serum malondialdehyde (MDA) content and decrease in serum superoxide dismutase (SOD) activity in mice. The results suggest that the antidepressant-like activity of DSS is probably mediated by the modulation of central monoamine neurotransmitter systems and the reduction of oxidative stress.

Anti-inflammation effect of Danggui Shaoyao San on Alzheimer's diseases

To study the mechanisms of Danggui Shaoyao San (DSS) on Alzheimer's diseases (AD) focusing on anti-inflammation. AD rats were established by intrahippocampal bilateral injection of Abeta1-42 protein. The AD rats were randomly divided into three groups: AD model group, DSS high-dose group, DSS low-dose group. Vehicle group rats were intrahippocampal bilateral injection of solvent with the same dose. The learning ability and memory of rats was investigated in step-down passive avoidance test and Morris water maze test, expression of IL-1beta, IL-6, TNF-alpha mRNA were observed by reverse transcriptase PCR (RT-PCR), levels of NO was measured by colorimetric method and neuron apoptosis in the hippocampus was investigated by tag method of TdT-mediated end-labeling of fragmented DNA (TUNEL). DSS significantly reduced the escape latency and increased the time that rats spent in the target quadrant in Morris water maze test, shortened the responsive latency and decreased the error numbers in step-down passive avoidance test, reduced the expression of the IL-1beta, IL-6, TNF-alpha mRNA, and the level of the NO depressed the neuron apoptosis in the hippocampus. DSS improving cognition of the rats might be related to attenuate inflammatory reaction and reduce cell apoptosis in the hippocampus.

JD-30, an active fraction extracted from Danggui–Shaoyao–San, decreases β-amyloid content and deposition, improves LTP reduction and prevents spatial cognition impairment in SAMP8 mice

JD-30 is an active fraction extracted from Danggui–Shaoyao–San (DSS), a traditional Chinese medicinal prescription. We previously showed that JD-30 could alleviate cognitive dysfunction of the mice induced by intracerebroventricular injection of β-amyloid (Aβ). However, data remain scarce on the effect of JD-30 on an Alzheimer's disease (AD) model and the underlying mechanisms are unknown. Further detailed studies on the effects of JD-30 on spatial cognition of senescence-accelerated mouse prone 8 (SAMP8), a suitable rodent model for cognitive impairment of aged subjects were investigated to elucidate the possible mechanisms. Long-term treatment with JD-30 significantly decreased the prolonged latency of SAMP8 in the Morris water-maze test. It also ameliorated the reduction of long-term potentiation (LTP) and reduced the damage of neurons in the hippocampus of SAMP8. Finally, JD-30 decreased the content and deposition of Aβ in the brain of SAMP8. The results show that JD-30 improves deterioration of spatial learning and memory in the SAMP8 mouse model, and by decreasing the content and deposition of Aβ, neuronal activity and synaptic plasticity improve, suggesting one of the mechanisms involved.

Identification and Determination of Absorbed Components of Danggui-Shaoyao-San in Rat Plasma

Aim To investigate the absorbed components of Danggui-Shaoyao-San (DSS) in rat plasma and their pharmacokinetics. Methods Serum samples from rats with DSS extract administrated orally were analyzed by HPLC-DAD-MS n and an HPLC-DAD method was established for the determination. Results Seven prototypes and one metabolite were identified in rat serum, and albiflorin, paeoniflorin, ferulic acid and ligustilide in rat plasma were determined for pharmacokinetic study. The proposed method was validated with a linear range of 0.025–5.60 μg·mL −1 and limit of quantitation (LOQ) at 0.022–0.180 μg·mL −1, respectively. The RSD of intra- and inter-day precision variations were less than 10.1% and the accuracies ranged from 92.5%–111.5%. The overall recovery was over 80%. Conclusion Paeoniflorin sulfonate, albiflorin, paeoniflorin, ferulic acid, senkyunolide I, ligustilide and butylidenephthalide were found to be the potentially effective constituents in DSS. The method for determination is simple and sensitive, which is proved to be suitable for pharmacokinetic study of albiflorin, paeoniflorin, ferulic acid and ligustilide in DSS.

Beneficial Effect of Traditional Chinese Medicinal Formula Danggui-Shaoyao-San on Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Diabetic Rats

The present study was undertaken to characterize the effects of Danggui-Shaoyao-San (DSS), a famous traditional Chinese medicine formula consisting of six herbal medicines, on diabetic nephropathy. Streptozotocin-induced diabetic rats were orally administrated DSS (2.8 g kg−1 per day) for 12 consecutive weeks. DSS partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-hour urinary albumin excretion rate, and creatinine clearance as well as the kidney hypertrophy (kidney weight/body weight ratio) and glomerular mesangial matrix expansion were ameliorated after 12 weeks of DSS treatment. The increased expression of nuclear factor-κB as well as transforming growth factor-β 1 and the progressive accumulation of type IV collagen in kidney of diabetic rats were also attenuated by DSS. Not only the elevated levels of advanced glycation end products (AGEs) and N ε-(carboxymethyl)lysine but also the higher levels of lipid peroxidation products in kidney of diabetic rats were ameliorated by DSS. Decreased activity of superoxide diamutase and glutathione peroxidase in kidney of diabetic rats was enhanced by DSS. These data demonstrated that the renoprotective effects of DSS in STZ-diabetic rats not only were attributable to regulate plasma glucose to attenuate AGEs expression in diabetic glomeruli but also likely reflected its antioxidant activity.

Pharmacokinetic properties of albiflorin and paeoniflorin after oral administration of pure compound, Radix Paeoniae alba extract and Danggui-Shaoyao-San extract to rats

This study compared the pharmacokinetics of albiflorin (ALB) and paeoniflorin (PAE), respectively, after oral administration of ALB, PAE, Radix Paeoniae alba (RPA) extract, and Danggui-Shaoyao-San (DSS) extract to rats on separate occasions. Analytes were detected simultaneously with liquid chromatography-tandem mass spectrometry. Noncompartmental pharmacokinetic parameters were calculated. After oral administration of RPA and DSS extract to rats, ALB reached maximum concentrations of 4637 ± 2774 ng/ml (0.40 ± 0.14 h) and 226 ± 122 ng/ml (0.35 ± 0.14 h) and PAE reached maximum concentrations of 2132 ± 560 ng/ml (0.40 ± 0.14 h) and 143 ± 65 ng/ml (0.45 ± 0.11 h), respectively. Compared to the AUC0 − t value (1122 ± 351 and 722 ± 158 ng h/ml for ALB and PAE, respectively) after administration of monomers, larger AUC0 − t value of ALB (4755 ± 2560 ng h/ml) and PAE (2259 ± 910 ng h/ml) after administration of RPA extract and smaller AUC0 − t value of ALB (411 ± 118 ng h/ml) and PAE (242 ± 126 ng h/ml) after administration of DSS extract were obtained. The C max, AUC, and K el of ALB and PAE were remarkably increased (P < 0.05, 0.01 or 0.005) during oral administration of RPA extract in comparison to that of DSS extract.

Comparative pharmacokinetics of paeoniflorin in plasma of vascular dementia and normal rats orally administrated with Danggui-Shaoyao-San or pure paeoniflorin

Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, is clinically used for the treatment of vascular dementia (VD). This study compared the pharmacokinetics of paeoniflorin, the main active ingredients in Paeonia lactiflora Pall, in VD and normal rats administrated with DSS or pure paeoniflorin. The absorptions of paeoniflorin in both VD and normal group of rats were better when orally administrated with DSS than that with pure paeoniflorin, which justified the combined use as formula DSS. Moreover, a better absorption of paeoniflorin in rats of the VD than in normal group was observed, which is helpful for the treatment of VD.

Hypothesis on the Principle of Danggui-Shao yao-San (DSS) for Treating Different Diseases via the Histamine H1 Receptor Pathway

Abstract The principle of “same treatment for different diseases” is the major reflection of treatment determination based on pathogenesis obtained through the differentiation of symptoms and signs in traditional Chinese medicine (TCM). It is of great importance to explore such principles from the viewpoint of TCM prescriptions, so as to propagate and develop TCM theory. Danggui-Shaoyao-San (DSS), a famous TCM complex prescription first recorded in the book of Jin Kui Yao Lue , has been widely used in the treatment for various diseases in China. Previous reference mining showed that its pathogenesis linked with “liver depression and spleen deficiency,” and there were a lot of similarities between pharmacological activities of DSS and the physiological and pathological function of histamine. This study suggested that DSS significantly inhibited local skin vascular permeability and remarkably decreased the scratching number and time, decreased locomotive activities increased by histamine, and exerted analgesia activities via the H1 receptor. A hypothesis has been proposed that DSS can modulate histamine H1 receptor expression and the relevant signal transduction pathway so as to treat various diseases, while “liver depression and spleen deficiency” would be related to the dysfunction of the histaminergic neuron system, whose regulating center is considered to be the histamine neurons located in the posterior hypothalamus based on a great deal of previous studies, casual findings, and international academic progress. Further investigation is under way to explore the principles or mechanism of DSS for treating different diseases, which may provide some new ideas or methods for the fundamental research of Integrated Chinese and Western Medicine. It provides some reference for reasonable and normative application of DSS in the clinic, accumulates new data for enriching scientific connotation of “liver depression and spleen deficiency” and the pathological mechanism of related diseases, and consequently academically enhances the TCM development.

Danggui-Shaoyao-San and its active fraction JD-30 improve Aβ-induced spatial recognition deficits in mice

Previous studies showed that Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients. However, the mechanism and substance basis remain unknown. JD-30 is a fraction extracted from DSS, whose activity we previously was evaluated. beta-Amyloid (Abeta) is believed to be a critical etiological factor of AD. We have now examined the effect of DSS and JD-30 on AD model mice induced by Abeta, and elucidated the possible mechanism. Mice were intracerebroventricular injected with the aggregated Abeta(25-35) to mimic AD. Groups of mice were treated with DSS or JD-30 by intragastric infusion over 2 weeks, and their spatial learning and memory capacities were measured by the Morris water maze procedure. The mechanisms were investigated by extracellular microelectrode recordings, and also electron microscopy. Our results show that Abeta(25-35) induced impairment of spatial learning and memory in mice, as well as inhibition of long-term potentiation (LTP) in the hippocampus. The impairments were ameliorated by DSS or JD-30 administration. Additionally, JD-30 not only prevented the aggregation of Abeta(25-35), but disrupted aggregated Abeta(25-35) fibrils. These results suggest that JD-30 is one of the chief active fractions extracted from DSS by its ability to ameliorate deterioration of cognition, and by blocking and disrupting the aggregation of Abeta so that synaptic plasticity was improved, which may be one of the mechanisms involved.

Identification and determination of the major constituents in Traditional Chinese Medicinal formula Danggui-Shaoyao-San by HPLC–DAD–ESI-MS/MS

Danggui-Shaoyao-San (DSS), a famous traditional Chinese medicine formula consisting of six herbal medicines ( Paeonia lactiflora, Angelica sinensis, Ligusticum chuanxiong, Poria cocos, Atractylodis macrocephalae and Rhizoma Alismatis), has been used as a classical gynecological remedy in China for centuries. However, its active substances have remained unknown. In this paper, an HPLC/DAD/ESI-MS/MS method was developed for the qualitative and quantitative analysis of the major constituents in DSS. The ESI-MS/MS fragmentation behavior of the reference compounds was proposed for aiding the structural identification of components in DSS extract. Forty-one compounds including monoterpene glycosides, phenolic acids, phathalides, sesquiterpenoids and triterpenes were identified or tentatively characterized by comparing their retention times, UV and MS spectra with those of authentic compounds or literature data, and 14 of them (gallic acid, albiflorin, paeoniflorin, ferulic acid, benzoic acid, senkyunolide I, coniferyl ferulate, senkyunolide A, 3-butylphthalide, Z-ligustilide, Z-butylidenephthalide, atractylcnolide II, atractylcnolide I and levistolide A) were determined by HPLC–DAD using a C 18 column and gradient elution of acetonitrile/water–formic acid (100:0.1, v/v). The linearity, precision, accuracy, LOD and LOQ were validated for the quantification method, which proved sensitive, accurate and reproducible. The study might provide a basis for the quality control of DSS extracts and preparations.

Age-related expression of calcium/calmodulin-dependent protein kinase II A in the hippocampus and cerebral cortex of senescence accelerated mouse prone/8 mice is modulated by anti–Alzheimer's disease drugs

Senescence-accelerated mouse (SAM) prone/8 (SAMP8) is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits such as Alzheimer's disease (AD) at the gene and protein levels, and SAM resistant/1 (SAMR1) is its normal control. Calcium/calmodulin-dependent protein kinase II-α (CaMKIIα) is one of the most abundant subunits of calcium/calmodulin-dependent protein kinase II in cerebral cortex and hippocampus, and is closely linked to AD. In this study, we used real time fluorescence quantitative PCR (RT-PCR) and Western blot techniques to examine the expression of CaMKIIα mRNA and protein in the cerebral cortex and hippocampus of SAMP8 both with aging and following treatment with anti-AD drugs (for example, natural product huperzine A (HupA) and traditional Chinese medicinal prescription Liu-Wei-Di-Huang decoction (LW), Ba-Wei-Di-Huang decoction (BW), Huang-Lian-Jie-Du decoction (HL), Dang-Gui-Shao-Yao-San (DSS) and Tiao-Xin-Fang decoction (TXF)). The results showed that the levels of both CaMKIIα mRNA and protein decreased significantly in the cerebral cortex of SAMR1 with aging, but increased significantly in the cerebral cortex of SAMP8. Compared with age-matched SAMR1, the expression of mRNA and protein of CaMKIIα significantly increased in the cerebral cortex and hippocampus of SAMP8 after 10 months of age. After SAMP8 was treated with the previously mentioned drugs, the abnormally high expression of CaMKIIα was relatively down-regulated. These results indicated that the expression of CaMKIIα in the brain of SAMP8 was abnormal and that this abnormality could be reversed with anti-AD drugs. These data suggest that CaMKIIα may play an important role in the age-related cognitive deterioration in AD, and may be a potential targets for anti-AD drugs.

Aqueous extract of the Chinese medicine, Danggui‐Shaoyao‐San, inhibits apoptosis in hydrogen peroxide‐induced PC12 cells by preventing cytochrome c release and inactivating of caspase cascade

Danggui-Shaoyao-San (DSS), a traditional Chinese medicine used for centuries for the enhancement of women's health, has been shown to display therapeutic efficacy on senile dementia. In the present study, using a rat pheochromocytoma (PC12) cell line, the effect of DSS on hydrogen peroxide (H2O2) induced apoptosis was studied. The apoptosis in H2O2-induced PC12 cells was accompanied by downregulation of Bcl-2, upregulation of Bax, the release of mitochondrial cytochrome c into cytosol, and sequential activation of caspase-9 and -3. DSS was able to suppress all these changes and eventually protected against H2O2-induced apoptosis. Taken together, these results suggest that treatment of PC12 cells with DSS can block H2O2-induced apoptosis by the regulation of Bcl-2 family members, as well as suppression of cytochrome c release and caspase cascade activation.

Neuroprotective effects of the aqueous extract of the Chinese medicine Danggui-Shaoyao-san on aged mice

Danggui-Shaoyao-san (DSS), a famous Chinese complex prescription, has been widely used for gynecological and obstetrical purposes for a long time, and recently it has gained much attention due to its therapeutic efficacy for senile dementia. In the present study, the effects of aqueous extract of Danggui-Shaoyao-san on naturally aged mice were examined to investigate the pharmacological basis for its therapeutic efficacy on senile dementia. The results showed that DSS significantly prolonged latency in a step-through test and increased brain index so as to improve impaired cognitive function of aged mice after oral administration at doses of 250 and 500 mg/kg for 3 months. Using high-performance liquid chromatography technique with electrochemical detection (HPLC-ECD), it was found that DSS increased the content of monoamine neurotransmitters such as norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in brains of aged mice. Using transmission electron microscope, it was found that DSS dose-dependently protected the ultrastructure of brain cortex in aged mice. These results indicate that DSS ameliorates memory dysfunction, modulates metabolism of monoamine neurotransmitters and protects the ultrastructure of cortex changed by aging. These findings suggest that DSS may be a useful therapeutic agent for senile dementia, especially Alzheimer's disease (AD).

Antioxidant and Antiplatelet Effects of Dang-Gui-Shao-Yao-San on Human Blood Cells

Dang-Gui-Shao-Yao-San (DGSYS) is a mixture of medicinal herbs, which has long been used in traditional Chinese medicine for treating anemia and ovulary disorders. Its preparation comprises Angelicae sinensis (Oliv.) Diels, Ligustucum chuanxiong Hort, Paeonia lactiflora pall, Poria cocos (Schw.) Wolf, Atractylodis macrocephala Koidz and Alisma orientalis (Sam.) Juzep. The present study examined the anti-superoxide formation, free radical scavenging and anti-lipid peroxidation activities of DGSYS by xanthine oxidase inhibition, cytochrome C system with superoxide anion released by the fMLP or PMA activating pathway in human neutrophils, and FeCl2 ascorbic acid-induced lipid peroxidation effects on lipids in rat liver homogenate, respectively. DGSYS showed anti-superoxide formation and free radical scavenging activity in a concentration-dependent manner. It also inhibited PMA- but not fMLP-induced superoxide anion released from human neutrophils. These antioxidant actions of DGSYS showed beneficial cytoprotective effects against lipid peroxidation in rat liver homogenate, human platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) and mitomycin C-mediated hemolytic in human erythrocytes.

A preliminary study on the radioprotection of mouse hematopoiesis by Dang-Gui-Shao-Yao-San

The purpose of this study reported here was to investigate the ability of Dang-Gui-Shao-Yao-San (DGSYS), known to elevate hematopoietic functions, to protect mice undergoing treatment with whole body single X-irradiation. DGSYS given at doses of 10 and 20 mg/20 g body weight, once a day, for 7 consecutive days before irradiation protected ICR strain mice from the sublethal effects of radiation in a dose-dependent manner. Prior administration of 20 mg/20 g DGSYS increased the number of femoral spleen colony-forming units (CFU-S) that survived irradiation, and significantly ameliorated leukopenia, thrombocytopenia and the degression of hematocrits after irradiation. These results suggest that DGSYS may be effective in the prevention of hematopoietic injury caused by sublethal dose irradiation.