Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

[CiteSpace knowledge map of research status and trends of Croci Stigma].

This study retrieved Croci Stigma related literature from CNKI, Wanfang, VIP, and Web of Science database, and used bibliometrics and CiteSpace 6.1.R2 software to analyze the published Croci Stigma related articles in Chinese and English from 2000 to 2022. The authors, research institutions, and keywords were visualized and analyzed, and the current status and development trend of Croci Stigma research was summarized by combining the information extraction methods. A total of 1 846 Chinese articles and 2 703 English articles were screened out and included. The results showed a generally steady increase in the number of Croci Stigma related articles. The results of the visualization analysis showed that there were more collaborations between researcher teams and major research institutions in English articles than Chinese articles. The Chinese articles was mainly published by China Pharmaceutical University, and most of the inter-institutional collaborations occurred in neighboring regions. The English articles was mainly published by Iranian institutions, and most of the cooperation occurred within the country, with less transnational cooperation. Keywords analysis showed that the research on Croci Stigma was mainly focused on chemical compositions, pharmacological effects, mechanisms, quality control, etc. It was predicted that the future research hotspots of Croci Stigma would mainly focus on pharmacological mechanism and clinical efficacy. The current research related to Croci Stigma still needs to be developed, cooperation should be strengthened, and more in-depth research should be conducted.

Medication rule of traditional Chinese medicine in the treatment of plateau hypoxia based on data mining. / 基于数据挖掘中药治疗高原性缺氧的组方规律.

OBJECTIVES: The development of traditional Chinese medicine (TCM) in the plateau area is relatively backward. There is a lack of system to analyze the effects of the special environment of plateau low pressure and hypoxia on human meridians qi and blood, as well as the etiology and pathogenesis of plateau hypoxic diseases. To analyze the composition rules of anti-hypoxia TCM formulation with data mining methods. METHODS: The experimental literatures related to high altitude hypoxia were searched in China National Knowledge Infrastructure (CNKI), Wanfang Med Online, VIP, China Biology Medicine disc and other databases, a standardized prescription database was established after screening and standardization of prescription data in the literature. The composition rules of these prescription including drug frequency, drug attributes, drug efficacy, drug combination, and core prescription were analyzed and displayed with visual charts. RESULTS: A total of 135 TCM prescriptions were included, and 229 flavored drugs were included. Among these prescriptions, the TCM with high frequency of use were Astragalus, Danshen, Ginseng, and Angelica, etc. Four natures of the TCM were mostly warm and calm. Five flavours of the TCM were mostly sweet, bitter, and pungent. And channel tropism of the TCM mostly entered the heart, lung, and liver meridians. The frequency combination of TCM was Astragalus-Danshen and Astragalus-Angelica. The core medicines of these prescriptions were Astragalus, Danshen, Angelica, Rhodiola, Goji, and Ginseng. TCM could alleviate symptoms such as chest tightness, chest pain, coughing and wheezing, coughing, vomiting, fatigue, and loss of appetite caused by hypoxia at high altitude. CONCLUSIONS: Through data mining, it is concluded that the prevention or treatment of plateau hypoxic diseases mostly utilized products can nourish blood, replenish qi and dispel stasis, and help yang and dispel qi, most of them are compatible with qi tonic drugs and blood circulation and stasis dissolving drugs, and pay attention to the combination of virtual and real, yin and yang.

Exercise performance reduction and preventive measures in highland sports. / 高原运动效能降低及防治措施.

The plateau is a special environment with low pressure, low oxygen, low temperature, and high ultraviolet radiation. The exercise performance of people on the plateau is generally reduced, which seriously affects the life and health of people living in the plateau and entering the plateau. In recent years, the prevention and treatment of injury caused by high altitude hypoxia has attracted wide attention. It has shown that the higher the altitude with the longer the duration of exercise, the faster the stationing, the greater the impact on people's sports performance. Rapid entry into the plateau and long-term stay in the plateau have an impact on people's explosive power, endurance and fine operation. Advances in medical technology enable various prevention methods to be used to acclimate to high altitude environments. However, in vitro intervention methods are costly, easy to rebound and possess limited effects. Therefore, drug prevention and treatment is obviously a more economical choice. Chemical drugs increase the efficiency of high altitude exercise by improving the ischemic and hypoxic symptoms of the heart and brain, increasing lung ventilation and arterial oxygenation capacity, and accelerating the elimination of adverse product accumulation after exercise. Single Chinese medicine, Chinese patent medicine, and compound preparations can improve exercise performance by promoting body metabolism, improving muscle endurance, enhancing immunity, and other mechanisms. Traditional Chinese medicine has unique advantage and application prospect in improving plateau sports performance damage.

[Comparison of distribution of verbascoside in normoxic and hypoxic rats].

This study established a high performance liquid chromatography(HPLC) method for the simultaneous determination of verbascoside(VB) and its main metabolite caffeic acid(CA) in rat tissue samples. A low-pressure low-oxygen animal experimental chamber was used to simulate the plateau environment for establishing the hypoxic rat model. After intragastric administration of 300 mg·kg~(-1) VB, the normoxic and hypoxic rats were sacrificed for the collection of heart, liver, spleen, lung, kidney, brain, muscle, large intestine, small intestine, and stomach tissue samples at the time points of 30, 60, and 90 min. VB and CA concentrations in each tissue sample were measured by HPLC, and the distribution of VB and CA in normoxic and hypoxic rats was compared. The results showed that after intragastric administration, VB can be rapidly absorbed and distributed into various tissues including brain in both normoxic and hypoxic rats, indicating that VB can pass through the blood-brain barrier. In the gastrointestinal tract, VB was mainly distributed in small intestine, which suggested that the main absorption site of VB was small intestine. A large amount of VB was detected in muscle and lung, and only a small amount in other tissues. CA was detected in other tissues except brain, heart, and muscle. Small intestine had the most abundant CA, followed by stomach, large intestine, and kidney, and only a small amount of CA was detected in the liver, spleen, and lung(<50 ng·mL~(-1)). The results indicated that VB may be mainly absorbed and metabolized in the gastrointestinal tract to produce CA and was possibly excreted through kidney. Compared with normoxic rats, hypoxic rats had reduced and slow distribution of VB and increased ratio of VB concentration in tissue to plasma, which implied that the relative proportion of VB from systemic circulation to tissues was increased in hypoxic rats. This study provides a basis for the application of VB in anti-hypoxia therapy and for the formulation of anti-hypoxia dosing regimens.

Effect of aqueous extract of Astragalus membranaceus on behavioral cognition of rats living at high altitude.

OBJECTIVE: To investigate the effect of aqueous extract of Astragalus membranaceus on cognitive ability of rats living at high altitude. METHODS: Rats were exposed to a simulated highaltitude hypobaric hypoxia chamber. The behavior of rats was tested by eight-arm maze. The contents of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) and activity of total superoxide dismutase (T-SOD) in hippocampus were measured. The expressions of mammalian target of rapamycin (mTOR) and cleaved capase-3 in hippocampus were determined by reverse transcription-polymerase chain reaction and Western blot. RESULTS: The behavioral cognitive ability of the hypoxic control group was significantly lower than that of the normoxic control group. Under hypoxic environment, after the administration of aqueous extract of Astragalus membranaceus, the behavioral cognitive ability of rats was significantly improved. In hippocampal tissue, the content of MDA and ROS were significantly decreased, while the content of GSH and activity of T-SOD in hippocampus were significantly increased. The mRNA expression of mTOR and P70S6K and the protein expression of p-mTOR were significantly increased; the mRNA expression of 4E-binding protein 1 (4E-BP1) and the protein expression of phosphorylated-4E-BP1 (p-4EBP1) and cleaved capase-3 were significantly decreased. CONCLUSION: When the rats are exposed to high altitude hypoxia, the behavioral cognitive ability could be significantly reduced. Aqueous extract of Astragalus membranaceus can significantly improve cognitive function in rats under hypoxia. The potential mechanism is related to improving oxidative stress, reducing the accumulation of free radicals and metabolites, and activating mTOR signaling pathway.

A review on the structure and pharmacological activity of phenylethanoid glycosides.

Phenylethanoid glycosides (PhGs) are compounds made of phenylethyl alcohol, caffeic acid and glycosyl moieties. The first published references about phenylethanoid glycosides concerned the isolation of echinacoside from Echinaceu ungustifolia (Asteraceae) in 1950 and verbascoside from Verbascum sinuatum (Scrophulariaceae) in 1963. Over the past 60 years, many compounds with these structural characteristics have been isolated from natural sources, and most of these compounds possess significant bioactivities, including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, and immunomodulatory activities, among others. In this review, we will summarize the phenylethanoid glycosides described in recent papers and list all the compounds that have been isolated over the past few decades. We will also attempt to present and assess recent studies about the separation, extraction, determination, and pharmacological activity of the excellent natural components, phenylethanoid glycosides.

Crocetin: A Systematic Review.

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin.

Gardenia jasminoides Ellis: Ethnopharmacology, phytochemistry, and pharmacological and industrial applications of an important traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia jasminoides Ellis is a popular shrub in the Rubiaceae family. The desiccative ripe fruits of this plant (called Zhizi in China) are well known and frequently used not only as an excellent natural colourant, but also as an important traditional medicine for the treatment of different diseases, such as reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis to activate blood circulation. It has also been declared as the first batch of dual-purpose plants used for food and medical functions in China. AIM OF THE STUDY: This review aims to provide a critical and systematic summary of the traditional uses, ethnopharmacology, phytochemistry, pharmacology, toxicity and industrial applications of Gardenia jasminoides Ellis and briefly proposes several suggestions for future application prospects. MATERIALS AND METHODS: The related information on Gardenia jasminoides Ellis was obtained from internationally recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of Science, Medline Plus, ACS, Elsevier and Flora of China) and libraries. RESULTS: Approximately 162 chemical compounds have been isolated and identified from this herb. Among them, iridoid glycosides and yellow pigment are generally considered the main bioactive and characteristic ingredients. Various pharmacological properties, such as a beneficial effect on the nervous, cardiovascular and digestive systems, hepatoprotective activity, antidepressant activity, and anti-inflammatory activity, were also validated in vitro and in vivo. Moreover, geniposide and genipin are the most important iridoid compounds isolated from Gardenia jasminoides Ellis, and genipin is the aglycone of geniposide. As the predominant active ingredient with a distinct pharmacological activity, genipin is also an outstanding biological crosslinking agent. Gardenia yellow pigment has also been widely used as an excellent natural dye-stuff. Hence, Gardenia jasminoides Ellis has been applied to many other fields, including the food industry, textile industry and chemical industry, in addition to its predominant medicinal uses. CONCLUSIONS: According to this review, Gardenia jasminoides Ellis is outstanding traditional medical plant used in medicine and food. Pharmacological investigations support the traditional use of this herb and may validate the folk medicinal use of Gardenia jasminoides Ellis to treat different diseases. Iridoid glycosides are potential medicines. Gardenia yellow pigment has been the most important source of a natural colourant for food, cloth and paint for thousands of years. This herb has made great contributions to human survival and development. Moreover, it has also achieved outstanding progress in human life and even in art. Although Gardenia jasminoides Ellis has extremely high and comprehensive utilization values, it is still far from being completely explored. Therefore, the comprehensive development of Gardenia jasminoides Ellis deserves further analysis.

Polysaccharide extracted from Potentilla anserina L ameliorate acute hypobaric hypoxia-induced brain impairment in rats.

High altitude cerebral edema (HACE) is a high altitude malady caused by acute hypobaric hypoxia (AHH), in which pathogenesis is associated with oxidative stress and inflammatory cytokines. Potentilla anserina L is mainly distributed in Tibetan Plateau, and its polysaccharide possesses many physiological and pharmacological properties. In the present study, the protective effect and potential treatment mechanism of Potentilla anserina L polysaccharide (PAP) in HACE were explored. First, we measured the brain water content and observed the pathological changes in brain tissues, furthermore, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH) were evaluated by kits. Finally, the protein contents and mRNA expressions of pro-inflammatory (IL-1ß, IL-6, TNF-α, vascular endothelial cell growth factor [VEGF], NF-κB, and hypoxia inducible factor-1 α [HIF-1α]) were detected by ELISA kits, RT-PCR, and western blotting. The results demonstrated that PAP reduced the brain water content, alleviated brain tissue injury, reduce the levels of MDA and NO, and increased the activity of SOD and GSH level. In addition, PAP blocking the NF-κB and HIF-1α signaling pathway activation inhibited the generation of downstream pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and VEGF). Therefore, PAP has a potential to treat and prevent of HACE by suppression of oxidative stress and inflammatory response.

Antioxidant activity and potential ameliorating effective ingredients for high altitude-induced fatigue from Gansu Maxianhao (Pedicularis Kansuensis Maxim.).

OBJECTIVE: To investigate the antioxidant property and potential ameliorating effective ingredients for high altitude-induced fatigue from Gansu Maxianhao (Pedicularis Kansuensis Maxim.). METHODS: Macroporous adsorptive resin combined with polyamide chromatographic column was used to obtain water extract (P1), high polar part (P2), iridoid glycosides part (P3) and phenylethanoid glycosides part (P4) of Gansu Maxianhao (Pedicularis Kansuensis Maxim.). Antioxidant activity of each part was investigated employing a series of in vitro models. Hematoxylin-eosin staining, analysis of blood biochemical parameters, along with molecular analyses examining oxidative stress makers, metabolite, metabolic enzyme and energy substance in liver, skeletal muscle and/or serum were further measured. RESULTS: The results showed phenylethanoid glycosides (PhGs) exhibited more effective with 1,1-diphenyl-2-picrylhydrazyl radical scavenging ability, 2-2-Azinbis (3-ehtylbenzothiazolin-6-sulfnicAcid) Diammonium Salt+ scavenging activity, hydroxyl radical scavenging activity, reducing ability and antioxidant activity to varying extents. Under a hypobaric hypoxia attack in a hypobaric chamber (8000 m, 7 consecutive days), PhGs was administered to BALB/C mice at doses of 50, 200, 400 mg/kg and antifatigue property was evaluated using a swimming test at an altitude of 4000 m. The results showed that PhGs of Gansu Maxianhao (Pedicularis Kansuensis Maxim.) could significantly prolong the burden swimming time of mice, reduce the hypoxia-induced oxidative stress, remove the accumulated products of metabolism, improve the energy metabolism as well as improve preservation of endogenous glycogen stores. CONCLUSION: The ameliorating effect against altitude-induced fatigue of PhGs from Gansu Maxianhao (Pedicularis Kansuensis Maxim.) might come from the alleviation of oxidative stress, reduction of the adverse metabolic products, normalizing energy metabolism and increasing energy substances reserves. PhGs is a potential antioxidant and novel remedy for fatigue due to high-altitude hypoxia.

Effect and mechanism of verbascoside on hypoxic memory injury in plateau.

Verbascoside is a water-soluble natural phenylethanoid glycoside and distributes widely in plants. It has been proved with antioxidant, neuroprotective, anti-inflammatory, antibacterial, and immunomodulatory bioactivities. In this experiment, the effect and mechanism of verbascoside on hypoxic memory injury were studied in a low-pressure and low-oxygen chamber. Verbascoside (50, 150, and 300 mg/kg) was intragastrically administered once a day for 7 days. On the fourth day, rats were placed in the chamber to simulate a 7,500 m high-altitude environment The eight-arm maze was used to test the memory ability. The levels of MDA, GSH, and T-SOD in plasma, brain-NH, and hippocampus were detected. The mRNA expression of mTOR, P70S6K, and 4E-BP1 in the hippocampus tissue was determined by PCR. The protein expression of P-mTOR, P-P70S6K, P-4E-BP1, and Cleaved Caspase-3 in the hippocampus tissue was determined by western blot. The results indicated that administration with verbascoside could obviously reduce the working memory error, reference memory error, total errors, and total time; relieve the neuron damage in CA1 region of the hippocampus; and decrease the oxidative stress correlation enzyme activity in plasma, brain, and hippocampus. The amelioration of verbascoside on high altitude-induced memory impairment may be associated with the adjustment of oxidative stress and mTOR signaling pathway.

Ethnomedicinal Uses, Phytochemistry, Pharmacology, and Toxicology of Species from the Genus Ajuga L.: A Systematic Review.

The present review is aimed at providing a comprehensive summary of the botanical characteristics, ethnomedicinal uses, phytochemical, pharmacological, and toxicological studies of the genus Ajuga L. The extensive literature survey revealed Ajuga L. species to be a group of important medicinal plants used for the ethnomedical treatment of rheumatism, fever, gout, sclerosis, analgesia, inflammation, hypertension, hyperglycemia, joint pain, palsy, amenorrhea, etc., although only a few reports address the clinical use and toxicity of these plants. Currently, more than 280 chemical constituents have been isolated and characterized from these plants. Among these constituents, neo-clerodane diterpenes and diterpenoids, phytoecdysteroids, flavonoids, and iridoids are the major bioactive compounds, possessing wide-reaching biological activities both in vivo and in vitro, including anti-inflammatory, antinociceptive, antitumor, anti-oxidant, antidiabetic, antimicrobial, antifeedant, antidiarrhoeal, hypolipidemic, diuretic, hypoglycaemic, immunomodulatory, vasorelaxant, larvicidal, antimutagenic, and neuroprotective activity. This review is aimed at summarizing the current knowledge of the ethnomedicinal uses, phytochemistry, biological activities, and toxicities of the genus Ajuga L. to reveal its therapeutic potentials, offering opportunities for future researches. Therefore, more focus should be paid to gathering information about their toxicology data, quality-control measures, and the clinical application of the bioactive ingredients from Ajuga L. species.

Phenylethanoid glycosides of Phlomis younghusbandii Mukerjee ameliorate acute hypobaric hypoxia-induced brain impairment in rats.

High altitude cerebral edema (HACE), whose development process is associated with oxidative stress and inflammatory response, is a life-threatening condition caused by rapid ascent speed to high altitudes. Phenylethanoid glycosides (PhGCs) are primary active constituents isolated from Phlomis younghusbandii Mukerjee that reportedly exhibit potent anti-oxidant and anti-inflammatory activities. The present study aims to investigate the protective effect of phenylethanoid glycosides (PhGCs) from P. younghusbandii in acute hypobaric hypoxia (AHH) - stimulated HACE rats and its underlying mechanisms. The expression of pro-inflammatory cytokine levels (IL-1ß, TNF-α, and IL-6) was detected by RT-PCR and ELISA at mRNA and protein levels in brain tissues. Western blotting was carried out to measure the major protein levels (IL-1ß, TNF-α, and NF-κB) in brain tissues. The oxidative stress biomarkers (MDA, SOD, and GSH) were evaluated using kits. Results demonstrate that PhGCs significantly improved pathological changes in brain tissues, reduced the brain's water content, and attenuated the production and mRNA expression of pro-inflammatory cytokines. Furthermore, the increased oxidative stress and the decrease in anti-oxidant stress system under the AHH condition were also abrogated reversely through PhGCs treatment by elevating the levels of SOD and GSH and suppressing the accumulation of MDA. Simultaneously, there was also a significant reduction in NF-κB, IL-1ß, and TNF-α protein expression levels in brain tissues, suggesting that blocking the NF-κB signaling pathway activation prevented the production of pro-inflammatory cytokines. Taken together, these findings indicate that PhGCs may afford a protectively intervene in HACE through the suppression of oxidative stress and inflammatory response via the inhibition of the NF-κB signaling pathway, indicating that PhGCs are promising agents for the treatment of acute HACE.

Traditional uses and pharmacological properties of Clerodendrum phytochemicals.

Clerodendrum is a genus of ca. 500 species in the family Lamiaceae and widely distributed throughout the whole world. Up to now, many species of this genus have been described in various indigenous systems of medicine and are used in preparation of folklore medicines for the treatment of various life-threatening diseases, and more than eleven species of the Clerodendrum genus have been very well studied for their chemical constituents and biological activities, and 283 compounds, including monoterpene and its derivatives, sesquiterpene, diterpenoids, triterpenoids, flavonoid and flavonoid glycosides, phenylethanoid glycosides, steroids and steroid glycosides, cyclohexylethanoids, anthraquinones, cyanogenic glycosides, and others have been isolated and identified. Pharmacological studies have shown that these compounds and extracts from the Clerodendrum genus have extensive activities, such as anti-inflammatory and anti-nociceptive, anti-oxidant, anti-hypertensive, anticancer, antimicrobial, anti-diarrheal, hepatoprotective, hypoglycemic and hypolipidemic, memory enhancing and neuroprotective, and other activities. In this review, we attempt to highlight over phytochemical progress and list the phytoconstituents isolated from the genus Clerodendrum reported so far. The biological activities of this genus are also covered.

Neu-P11, a novel MT1/MT2 agonist, reverses diabetes by suppressing the hypothalamic-pituitary-adrenal axis in rats.

Excessive glucocorticoid (GC) in type 2 diabetes mellitus (T2DM) reduces insulin sensitivity, impairs ß-cell function, increases gluconeogenesis and glycogenolysis, impairs glucose uptake and metabolism, and reduces the insulinotropic effects of glucagon-like peptide 1. Melatonin, which serves as a physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis, has been suggested to have anti-diabetic effects. The objective of the present study was to investigate the effect of the MT1/MT2 melatonin agonist Neu-P11 on glucose and lipid metabolism in T2DM rats induced by a high fat diet combined with low doses of streptozotocin. T2DM rats were intragastrically administered melatonin (20mg/kg), Neu-P11 (20, 10, 5mg/kg), or a vehicle for 4 weeks. The results showed that the increased food intake, water consumption, hyperglycemia, glucose intolerance, and insulin resistance in T2DM rats were all improved by Neu-P11 treatment. Neu-P11 increased GC receptor expression and suppressed 11ß-hydroxysteroid dehydrogenase 1 activity in the hippocampus by enhancing GC sensitivity and HPA feedback, thus decreasing the high GC levels. Transcript levels of the glucose metabolism-related genes peroxisome proliferator-activated receptor-γ, glucose transporter type-4, and adiponectin in adipose tissue were significantly increased after Neu-P11 treatment, while leptin mRNA was significantly decreased. Furthermore, MT1 and MT2 protein levels were enhanced by Neu-P11. These data suggest that normalization of the hyperactivated HPA axis by melatonin and Neu-P11 in T2DM regulates metabolic profiles and insulin sensitivity, which may attenuate insulin resistance and glucose homeostasis. Because Neu-P11 has superior pharmacokinetics and a longer half-life than melatonin, it might be beneficial in treating obesity and T2DM.

The Genus Patrinia: A Review of Traditional Uses, Phytochemical and Pharmacological Studies.

The aim of the present review is to comprehensively outline the botanical description, traditional uses, phytochemistry, pharmacology and toxicology of Patrinia, and to discuss possible trends for the further study of medicinal plants from the genus Patrinia. The genus Patrinia plays an important role in Asian medicine for the treatment of erysipelas, conjunctival congestion with swelling and pain, peri-appendicular abscesses, lung carbuncle, dysentery, leucorrhea, and postpartum disease. More than 210 chemical constituents have been isolated and identified from Patrinia plants, especially P. scabiosaefolia Fisch., P. scabra Bunge, P. villosa Juss., P. heterophylla Bunge and P. rupestris(Pall.) Juss[Formula: see text] Of these compounds, triterpenoids and saponins, iridoids, flavonoids, and lignans are the major or active constituents. Both in vitro and in vivo studies have indicated that some monomer compounds and crude extracts from the genus Patrinia possess wide pharmacological activities, including antitumor, anti-inflammatory, antibacterial, and antiviral effects. In addition, they have been shown to have valuable and positive effects on the immune and nervous system in experimental animals. There are also some reports on the clinical uses and toxicity of these species. However, few reports have been published concerning the material identification or quality control of Patrinia species, and the clinical uses and toxic effects of these plants are relatively sparse. More attention must be given to these issues.

A new anti-fibrinolytic hemostatic compound 8-O-acetyl shanzhiside methylester extracted from Lamiophlomis rotata.

BACKGROUND: Fibrinolysis prevents blood clots from growing and becoming problematic. Antifibrinolytics are used as inhibitors of fibrinolysis. Aprotinin was doubted after identification of major side effects, especially on kidney. Lysine analogues has their own defects and whether they are adequate substitutes for aprotinin is still under doubt. Lamiophlomis rotata (Benth.) Kudo. was previous found to have hemostatic activity. But the active compound in L. rotata and its hemostatic mechanism were unknown. OBJECTIVES: To find the major hemostatic compound in L. rotata and identify its haemostasis mechanism. METHODS: Traumatic hemorrhage model and coagulant activity assays were monitored in mice and platelets in drug treatment group and control group. Hyperfibrinolysis model was established by intravenous administration of urokinase in mice. Capillary blood clotting time (CBCT), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen and euglobulin clot lysis time (ECLT) were measured. RESULTS: The anti-fibrinolytic activity come from 8-O-Acetyl shanzhiside methylester (ASM) one of the highest iridoid glycosides contents in TIG extracted from L. rotata. ASM significantly (P<0.05) shorten CBCT and reduced blood loss volume in vivo, but did not influence mice APTT, PT or TT. In particular, it significantly prolonged ECLT in hyperfibrinolysis mice. It indicated that ASM could inhibit fibrinolysis. ASM was also effective in CBCT, traumatic bleeding volume and ECLT in hyperfibrinolysis mice model. CONCLUSIONS: ASM was the major hemostatic compound in L. rotata. The haemostasis mechanism of ASM was achieved by anti-fibrinolytic activity. ASM was a new fibrinolysis inhibitor as iridoid glycoside compound.

Phenylethanoid glycosides of Pedicularis muscicola Maxim ameliorate high altitude-induced memory impairment.

Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment.