Shexiang Baoxin Pill, a Proprietary Multi-Constituent Chinese Medicine, Prevents Locomotor and Cognitive Impairment Caused by Brain Ischemia and Reperfusion Injury in Rats: A Potential Therapy for Neuropsychiatric Sequelae of Stroke.

Ischemic stroke is a common type of cerebrovascular event and also the leading cause of disability. Post-stroke cognitive impairment occurs frequently in stroke survivors. Shexiang Baoxin Pill (SBP) is a proprietary Chinese medicine, initially used to treat cardiovascular diseases. Herein, we aim to explore the effects of SBP on oxygen glucose deprivation and reoxygenation (OGD/R) in neuronal cells (CATH.a) and cerebral ischemia/reperfusion injury induced post-stroke cognitive impairment in middle cerebral artery occlusion (MCAO) rat model. MCAO rats received two doses of oral SBP treatment (28 or 56 mg/kg) after 1 h of operation and once daily for 2 weeks continuously. Behavioral tests, immunoblotting, and immunofluorescence were examined after 14 days. Current data suggest that SBP enhanced cell viability and downregulated apoptosis via activating the PI3K/Akt signaling pathway in CATH. a cells. Furthermore, 14 days of SBP treatment promoted the recovery of learning and locomotor function in the MCAO rats. SBP up-regulated the expression of p-Akt, p-GSK3ß, as well as the expression of NMDAR1, PSD-95, and AMPAR. Also, SBP down-regulated the expression of p-CaMKII. These results indicated that long-term SBP treatment might be a potential option for cognitive impairment induced by the ischemic stroke.

Jie-Yu Pill, A Proprietary Herbal Medicine, Ameliorates Mood Disorder-Like Behavior and Cognitive Impairment in Estrogen-Deprived Mice Exposed to Chronic Unpredictable Mild Stress: Implication for a Potential Therapy of Menopause Syndrome.

Jie-Yu Pill (JYP) is a proprietary herbal medicine initially developed to treat menstrual mood disorders. This study sought to determine whether JYP could alleviate menopausal psychiatric symptoms in ovariectomized (OVX) mice, an animal model of estrogen deprivation, exposed to chronic unpredictable mild stress (CUMS) and the underlying mechanisms in comparison with estrogen therapy. The OVX+CUMS mice were treated with 0.3 mg/kg estradiol (E2), 2.5 g/kg or 5 g/kg JYP for 36 days, and tested in multiple behavioral paradigms. Serum, uterus, and brain tissues were collected for the measurement of hypothalamus-pituitary-ovarian axis (HPO) and hypothalamus-pituitary-adrenal (HPA) axis hormones, γ-aminobutyric acid (GABA), glutamate, neurotrophins, and estrogen receptors. JYP and E2 had comparable efficacy in reducing anxiety- and depression-like behavior and cognitive impairment of the OVX+CUMS mice. E2 strikingly increased ratio of uterus to body weight of the OVX+CUMS mice, but JYP did not. Both agents suppressed HPO-axis upstream hormones, inhibited HPA-axis hyperactivity by reinstating hypothalamic GABA, restored hippocampal and prefrontal glutamate contents and its receptor expression in the OVX+CUMS mice. While JYP and E2 protected against decreases in hippocampal and prefrontal neurotrophins and estrogen receptors of the OVX+CUMS mice, unlike E2, JYP had no significant effects on these biomarkers in the uterus. These results suggest that JYP has comparable efficacy in ameliorating mood disorder-like behavior and cognitive impairment induced by a combination of estrogen deprivation and chronic stress in association with certain differential uterus-brain mechanisms compared to estrogen therapy. JYP may be a potential therapy for menopause-associated psychiatric disorders.

Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy.

Our previous study has demonstrated the effects of aqueous extract of lily bulb in alleviating menopause-related psychiatric symptoms in ovariectomized (OVX) mice. This study sought to further investigate the psychotropic effects of total polysaccharides of lily bulb (TPLB) against anxiety, depression, and cognitive deterioration and the underlying mechanisms in OVX mice using behavioral, neurochemical, molecular, and proteomic approaches in comparison with estrogen therapy. While TPLB and estradiol showed similar effects in reducing OVX-induced anxiety, depression, and cognitive impairment, the psychotropic effects of TPLB were more closely associated with the predominant activation of estrogen receptors (ERs) and regulation of brain regional neurotransmitters and neurotrophins with minor effects on the uterus. Estradiol had similar potencies in binding affinity at ERα and ERß, which caused widespread genetic and epigenetic effects. In contrast, TPLB displayed a higher affinity at ERß than ERα, triggering the specific Ras/Akt/ERK/CREB signaling pathway without affecting any epigenetic activity. TPLB additionally modulated multiple proteins associated with mitochondrial oxidative stress, but estradiol did not. These results indicate that TPLB has comparable efficacy in reducing menopause-associated neuropsychological symptoms with a better safety profile compared to estrogen therapy. We suggest that TPLB could serve as a novel agent for menopause syndrome.

Ameliorative effects of Radix rehmanniae extract on the anxiety- and depression-like symptoms in ovariectomized mice: A behavioral and molecular study.

BACKGROUND: Menopause is closely associated with the risk of anxiety and depression in a woman's life. Despite the numerous reports on the effects of Radix rehmanniae extract (RRE) on various types of depression, there are few studies exploring the effects of RRE on the menopausal anxiety and depression. PURPOSE: To investigate whether RRE could alleviate the menopausal anxiety and depression in ovariectomized (OVX) mice submitted to chronic unpredictable mild stress (CUMS). METHODS: OVX mice were treated with 2.6 g/kg RRE for 5 weeks. After a series of behavior tests, serum, uterus, and brain tissues were collected for the measurement of neurotransmitters and their related biomarkers, neurotrophins, and estrogen receptor α (ERα) and ß (ERß). RESULTS: RRE showed antidepressant and anxiolytic effects through these behavior tests, but had no effects on the OVX-induced weight gains, uterine shrinkage and drop of serum estrogen level. RRE restored the levels of serotonin (5-HT), dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), Glutamate (Glu), gamma-Aminobutyric acid (GABA) and their related biomarkers in different brain regions. RRE also reversed OVX-induced decrease in the expression levels of neurotrophins in uterus and brain regions except for uterine nerve growth factor (NGF). Moreover, RRE restored and even enhanced ERß expression levels in uterus and brain without affecting uterine, hippocampal and cortical ERα. CONCLUSION: This study demonstrated the antidepressant and anxiolytic effects of RRE in OVX mice, which were possibly mediated via their modulation of brain neurotransmitters, and regulation of neurotrophins and activation of ERß.

Aqueous extract of lily bulb ameliorates menopause-like behavior in ovariectomized mice with novel brain-uterus mechanisms distinct from estrogen therapy.

BACKGROUND: Lily bulb is often used as a dietary supplement for menopause. This study was aimed to investigate the ameliorative effects of aqueous extract of lily bulb (AELB) on the menopause-associated psychiatric disorders and the underlying mechanisms in comparison with estrogen therapy. METHODS: Ovariectomized (OVX) mice were treated with 1.8 g/kg AELB or 0.3 mg/kg estradiol for 5 weeks. Animals were tested in multiple behavioral paradigms. Serum, uterus, and brain tissues were collected for the measurement of neurotransmitters and their related biomarkers, neurotrophins, and estrogen receptor α (ERα) and ß (ERß). RESULTS: AELB and estradiol had similar anxiolytic, antidepressant, and cognition-improving effects. While estradiol limited OVX-induced weight gains and prevented uterine shrinkage and the drop of serum estrogen level, AELB had minor and even no effects on these indices. AELB, but not estradiol, reversed OVX-induced decreases in the expression levels of hippocampal nerve growth factor (NGF) and prefrontal glial cell-derived neurotrophic factor (GDNF). In addition to hypothalamic and prefrontal ERα, AELB enhanced uterine and brain regional ERß expression levels without affecting uterine ERα, NGF, and GDNF. Conversely, estradiol completely restored the expression levels of estrogen receptors and neurotrophins in uterus. CONCLUSIONS: While AELB is comparable to estradiol in alleviating menopause-like behavior, it has distinct brain-uterus mechanisms in association with the predominant protection of catecholamine synthesis, neurotrophins, and ERß receptors in brain, but with minor effects on uterus. AELB and its constituents may be novel treatments for menopause.

Antidepressant and anxiolytic effects of the proprietary Chinese medicine Shexiang Baoxin pill in mice with chronic unpredictable mild stress.

Depression and anxiety often co-occur with cardiac diseases. The Shexiang Baoxin pill (SBP) is a proprietary Chinese medicine initially used to treat cardiac conditions. This study explored whether SBP has antidepressant and anxiolytic effects in addition to hormonal and psychotropic mechanisms. Mice underwent 6 weeks of chronic unpredictable mild stress (CUMS) to induce depression- and anxiety-like behavior. During the 6-week experiment, mice received SBP at intragastric doses of 20.25 mg/kg or 40.5 mg/kg daily. Animals were then tested for depression in sucrose preference, forced-swimming, and tail suspension paradigms, and for anxiety in open field and elevated plus maze tests. Both SBP doses significantly reduced anhedonic behavior in the sucrose preference test; the high SBP dose also increased the number of entries into the central zone of the open field. SBP-treated mice had markedly lower blood levels of corticotrophin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) than stressed mice treated with vehicle. Either low- or high-dose SBP reversed stress-induced reductions of norepinephrine (NE) and dopamine (DA) metabolites and the expression levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF) in related brain regions. These results suggest that SBP could prevent and alleviate prolonged stress-induced anhedonia and anxiety in association with its suppression of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, modulation of brain monoamine neurotransmitter metabolism and neurotrophins. SBP may be particularly suitable for the management of depressive and anxiety disorders in patients with cardiac conditions.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.

Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burk.) F.H. Chen is a widely used traditional Chinese medicine known as Sanqi or Tianqi in China. This plant, which is distributed primarily in the southwest of China, has wide-ranging pharmacological effects and can be used to treat cardiovascular diseases, pain, inflammation and trauma as well as internal and external bleeding due to injury. AIMS OF THE REVIEW: This paper provides up-to-date information on investigations of this plant, including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. The possible uses and perspectives for future investigation of this plant are also discussed. MATERIALS AND METHODS: The relevant information on Panax notoginseng (Burk.) F.H. Chen was collected from numerous resources, including classic books about Chinese herbal medicine, and scientific databases, including Pubmed, SciFinder, ACS, Ebsco, Elsevier, Taylor, Wiley and CNKI. RESULTS: More than 200 chemical compounds have been isolated from Panax notoginseng (Burk.) F.H. Chen, including saponins, flavonoids and cyclopeptides. The plant has pharmacological effects on the cardiovascular system, immune system as well as anti-inflammatory, anti-atherosclerotic, haemostatic and anti-tumour activities, etc. CONCLUSIONS: Panax notoginseng is a valuable traditional Chinese medical herb with multiple pharmacological effects. This review summarizes the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of P. notoginseng, and presents the constituents and their corresponding chemical structures found in P. notoginseng comprehensively for the first time. Future research into its phytochemistry of bio-active components should be performed by using bioactivity-guided isolation strategies. Further work on elucidation of the structure-function relationship among saponins, understanding of multi-target network pharmacology of P. notoginseng, as well as developing its new clinical usage and comprehensive utilize will enhance the therapeutic potentials of P. notoginseng.

[Discrimination of Descurainiae Semen and Pantagirus Semen by HPLC fingerprints].

OBJECTIVE: To discriminate Descurainiae Semen and Pantagirus Semen. METHOD: A high-performance liquid chromatographic method was developed to establish the fingerprint of Descurainiae Semen, and hierarchical cluster analysis (HCA) and partial least squares discriminant analysis (PLS-DA) were applied to study HPLC fingerprinting and chemical recognition. RESULT: There exists large difference of chromatographic peaks and its relative peak area of HPLC fingerprints between Descurainiae Semen and Pantagirus Semen, and after conducting statistical analysis, the result demonstrated that all samples were classified into three categories: Descurainiae Semen, Pantagirus Semen and their mixtures. CONCLUSION: The developed HPLC fingerprint combined with chemometrics can be utilized to discriminate between Descurainiae Semen and Pantagirus Semen, which was quick, simple, accurate and reliable an can provide the basis for the characterization and quality assess of Descurainiae Semen and Pantagirus Semen.

Discrimination of Semen cassiae from two related species based on the multivariate analysis of high-performance liquid chromatography fingerprints.

A simple and efficient high-performance liquid chromatography fingerprint method was developed to discriminate Semen cassiae from two related species: Cassia obtusifolia L. (CO) and Cassia tora L. (CT), the seeds of which are abbreviated as COS and CTS, respectively. 22 major bioactive ingredients in 42 samples (20 COS and 22 CTS) collected from different provinces of China were identified. The statistical methods included similarity analysis and partial least-squares discriminant analysis. The pattern analysis method was specific and could be readily used for the comprehensive evaluation of Semen cassiae samples. Therefore, high-performance liquid chromatography fingerprint in combination with pattern analysis provided a simple and reliable method for discriminating between COS and CTS.

Chemometric analyses for the characterization of raw and processed seeds of Descurainia sophia (L.) based on HPLC fingerprints.

The seeds of Descurainia sophia (L.) (short for DSS below), with a long history of medicinal utilization in China, have attracted the attention of many Chinese medicine practitioners for the potent efficacy. In the present study, the raw and processed DSS were differentiated by several chemometrics methods based on HPLC fingerprints. Moreover, peaks which were mainly responsible for the differentiation between raw and roasted DSS were found. Therefore, the method of the chromatographic fingerprints combined with multivariate statistical analysis was effective and reasonable in orientating chemical constituents which were mainly responsible for the differentiation between raw and roasted materials, thus shedding light on illustrating the processing mechanism. What's more, this method can also be applied in the identification of authenticity.

Five new anthraquinones from the seed of Cassia obtusifolia.

A phytochemical investigation on the seeds of Cassia obtusifolia led to the isolation of five new anthraquinones, including one aglycon and four glycosides. The structures were elucidated by analysis of extensive spectroscopic data and the results of acid hydrolysis. All these isolates were evaluated for their inhibitory effects against α-glucosidase, and 1 showed potent activity with IC50 value of 185 ± 15 µM.

A review on phytochemistry and pharmacological activities of the processed lateral root of Aconitum carmichaelii Debeaux.

ETHNOPHARMACOLOGICAL RELEVANCE: The processed lateral root of Aconitum carmichaelii Debeaux (Ranunculaceae), an extensively used traditional Chinese medicine, is known as Fuzi in China (Chinese: ), "bushi" in Japan, "Kyeong-Po Buja" in Korea, Chinese aconite, monkshood or Chinese wolfsbane. It has been used to treat shock resulting from acute myocardial infarction, low blood pressure, coronary heart disease, chronic heart failure, etc. AIM OF THE REVIEW: The present paper aims to provide an up-to-date review at the advancements of the investigations on the ethnopharmacology, phytochemistry, pharmacological effect and toxicity of Fuzi. Besides, the possible tendency and perspective for future research of this plant are discussed, as well. MATERIALS AND METHODS: All available information on Fuzi was collected via electronic search (using Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, and Web of Science), books and classic works about Chinese herb. RESULTS: 122 chemical constituents, among which C19-diterpenoid alkaloids and C20-diterpenoid alkaloids are the predominant groups, have been isolated and identified from Fuzi. Fuzi with its active compounds is possessed of wide-reaching biological activities, including effects on cardiovascular system, anti-inflammation and analgesic action, anti-tumor activity, effect on the immune system, hypoglycemic and hypolipidemic effects, anti-aging effect, effect of protecting kidney and effect on energy metabolism. CONCLUSIONS: Nearly all of compounds were found from the roots of the plant, so further phytochemical studies should focus more on the other parts of the plant, such as the leaves, flowers or stems. Besides, a majority of the pharmacological studies were carried out using crude and poorly characterized extracts. Thus, more bioactive components particularly cardiotonic and analgesic compounds should be identified through bioactivity-guided isolation strategies. Moreover, investigations on how to develop Fuzi׳s new clinical usage on the basis of its pharmacological effects are in requirement.

[Advances on Lepidii Semen and Descurainiae Semen].

"Tinglizi", the ripe seed of Descurainia sophia and Lepidium apetalum, is a member of Brassicaceae (Cruciferae). Traditionally, the former is called "Nantinglizi" (Descurainiae Semen) while the latter is called "Beitinglizi" (Lepidii Semen). In the theory of traditional Chinese medicine, it has the power to purge lung-fire, relieve dyspnea, promote diuresis and reduce edema, and it is mainly indicated in a case with phlegm-fluid accumulation, cough with excessive sputum, dyspnea with being unable to lie, and general swelling. In view of its wide-spread application in clinic, a comprehensive review of Lepidii Semen and Descurainiae Semen was conducted from the following aspects: herbalogical study, variety identification, historical evolution of processing, chemical constituents, pharmacological effects, quantitative determination and toxicity which could provide reference for further research and development of "Tinglizi".

Towards a better understanding of medicinal uses of Carthamus tinctorius L. in traditional Chinese medicine: a phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Carthamus tinctorius L. (Compositae), a widely used traditional Chinese medicine, was known as Hong hua (Chinese: ), safflower. Safflower with a wide spectrum of pharmacological effects has been used to treat dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, trauma and pain of joints, etc. The present paper reviews the advancements in investigation of botany and ethnopharmacology, phytochemistry, pharmacology and toxicology of safflower. Finally, the possible tendency and perspective for future investigation of this plant are discussed, too. MATERIALS AND METHODS: The information on safflower was collected via piles of resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, Google Scholar, ACS, Web of science, CNKI and others. RESULTS: Over 104 compounds from this plant have been isolated and identified, and quinochalcones and flavonoids are considered as the characteristic and active constituents of safflower. Safflower with its active compounds possesses wide-reaching biological activities, including dilating coronary artery, improving myocardial ischemia, modulating immune system, anticoagulation and antithrombosis, antioxidation, antiaging, antihypoxia, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. CONCLUSIONS: As an important traditional Chinese medicine, it is important to investigate the pharmacological effects and molecular mechanisms of this plant based on modern realization of diseases' pathophysiology. More bioactive components should be identified using bioactivity-guided isolation strategies, and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from safflower need to be evaluated integrating pharmacological, pharmacokinetic, bioavailability-centered and physiological approaches. Further studies on safflower can lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attention to.