Astragalin: a food-origin flavonoid with therapeutic effect for multiple diseases.

Naturally occurring flavonoids have long been utilized as essential templates for the development of novel drugs and as critical ingredients for functional foods. Astragalin (AG) is a natural flavonoid that can be isolated from a variety of familiar edible plants, such as the seeds of green tea, Morus alba L., and Cuscuta chinensis. It is noteworthy that AG has a wide range of pharmacological activities and possesses therapeutic effects against a variety of diseases, covering cancers, osteoarthritis, osteoporosis, ulcerative colitis, mastitis, obesity, diabetes mellitus, diabetic complications, ischemia/reperfusion injury, neuropathy, respiratory diseases, and reproductive system diseases. This article reviewed the natural source and pharmacokinetics of AG and systematically summarized the pharmacological activities and potential mechanisms of AG in treating diverse diseases in order to promote the development of AG as a functional food, in doing so providing references for its clinical application in disease therapy.

Could Cyclosiversioside F Serve as a Dietary Supplement to Prevent Obesity and Relevant Disorders?

Obesity is the basis of numerous metabolic diseases and has become a major public health issue due to its rapidly increasing prevalence. Nevertheless, current obesity therapeutic strategies are not sufficiently effective, so there is an urgent need to develop novel anti-obesity agents. Naturally occurring saponins with outstanding bio-activities have been considered promising drug leads and templates for human diseases. Cyclosiversioside F (CSF) is a paramount multi-functional saponin separated from the roots of the food-medicinal herb Astragali Radix, which possesses a broad spectrum of bioactivities, including lowering blood lipid and glucose, alleviating insulin resistance, relieving adipocytes inflammation, and anti-apoptosis. Recently, the therapeutic potential of CSF in obesity and relevant disorders has been gradually explored and has become a hot research topic. This review highlights the role of CSF in treating obesity and obesity-induced complications, such as diabetes mellitus, diabetic nephropathy, cardiovascular and cerebrovascular diseases, and non-alcoholic fatty liver disease. Remarkably, the underlying molecular mechanisms associated with CSF in disease therapy have been partially elucidated, especially PI3K/Akt, NF-κB, MAPK, apoptotic pathway, TGF-ß, NLRP3, Nrf-2, and AMPK, with the aim of promoting the development of CSF as a functional food and providing references for its clinical application in obesity-related disorders therapy.

Galangin: A food-derived flavonoid with therapeutic potential against a wide spectrum of diseases.

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.

[Research progress on mechanism of Carthamus tinctorius in ischemic stroke therapy].

Carthamus tinctorius is proved potent in treating ischemic stroke. Flavonoids, such as safflower yellow, hydroxysafflor yellow A(HSYA), nicotiflorin, safflower yellow B, and kaempferol-3-O-rutinoside, are the main substance basis of C. tinctorius in the treatment of ischemic stroke, and HSYA is the research hotspot. Current studies have shown that C. tinctorius can prevent and treat ischemic stroke by reducing inflammation, oxidative stress, and endoplasmic reticulum stress, inhibiting neuronal apoptosis and platelet aggregation, as well as increasing blood flow. C. tinctorius can regulate the pathways including nuclear factor(NF)-κB, mitogen-activated protein kinase(MAPK), signal transducer and activator of transcription protein 3(STAT3), and NF-κB/NLR family pyrin domain containing 3(NLRP3), and inhibit the activation of cyclooxygenase-2(COX-2)/prostaglandin D2/D prostanoid receptor pathway to alleviate the inflammatory development during ischemic stroke. Additionally, C. tinctorius can relieve oxidative stress injury by inhibiting oxidation and nitrification, regulating free radicals, and mediating nitric oxide(NO)/inducible nitric oxide synthase(iNOS) signals. Furthermore, mediating the activation of Janus kinase 2(JAK2)/STAT3/suppressor of cytokine signaling 3(SOCS3) signaling pathway and phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt)/glycogen synthase kinase-3ß(GSK3ß) signaling pathway and regulating the release of matrix metalloproteinase(MMP) inhibitor/MMP are main ways that C. tinctorius inhibits neuronal apoptosis. In addition, C. tinctorius exerts the therapeutic effect on ischemic stroke by regulating autophagy and endoplasmic reticulum stress. The present study reviewed the molecular mechanisms of C. tinctorius in the treatment of ischemic stroke to provide references for the clinical application of C. tinctorius.

Pharmacological Activities of Safflower Yellow and Its Clinical Applications.

Background: Safflower is an annual herb used in traditional Chinese herbal medicine. It consists of the dried flowers of the Compositae plant safflower. It is found in the central inland areas of Asia and is widely cultivated throughout the country. Its resistance to cold weather and droughts and its tolerance and adaptability to salts and alkalis are strong. Safflower has the effect of activating blood circulation, dispersing blood stasis, and relieving pain. A natural pigment named safflower yellow (SY) can be extracted from safflower petals. Chemically, SY is a water-soluble flavonoid and the main active ingredient of safflower. The main chemical constituents, pharmacological properties, and clinical applications of SY are reviewed in this paper, thereby providing a reference for the use of safflower in preventing and treating human diseases. Methods: The literature published in recent years was reviewed, and the main chemical components of SY were identified based on chemical formula and structure. The pharmacological properties of hydroxysafflor yellow A (HSYA), SYA, SYB, and anhydrosafflor yellow B (AHSYB) were reviewed. Results: The main chemical constituents of SY included HSYA, SYA, SYB, and AHSYB. These ingredients have a wide range of pharmacological activities. SY has protective effects on the heart, kidneys, liver, nerves, lungs, and brain. Moreover, its effects include, but are not limited to, improving cardiovascular and cerebrovascular diseases, abirritation, regulating lipids, and treating cancer and diabetic complications. HSYA is widely recognised as an effective ingredient to treat cardiovascular and cerebrovascular diseases. Conclusion: SY has a wide range of pharmacological activities, among which improving cardiovascular and cerebrovascular diseases are the most significant.

Pharmacological activities and pharmacokinetics of liquiritin: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Liquiritin is a flavonoid derived from Radix et Rhizoma Glycyrrhizae, which is a widely used traditional Chinese medicine with the effects of invigorating spleen qi, clearing heat, resolving toxins, and dispelling phlegm to stop coughs. AIM OF THE STUDY: In this review,the pharmacokinetics and pharmacological activities of liquiritin have been summarized. MATERIALS AND METHODS: The information on liquiritin up to 2021 was collected from PubMed, Web of Science, Springer Link, and China National Knowledge Infrastructure databases. The key words were "liquiritin", "nerve", "tumor", "cardiac", etc. RESULTS: The absorption mechanism of liquiritin conforms to the passive diffusion and first-order kinetics while with low bioavailability. Liquiritin can penetrate the blood-brain-barrier. Besides, liquiritin displays numerous pharmacological effects including anti-Alzheimer's disease, antidepressant, antitumor, anti-inflammatory, cardiovascular protection, antitussive, hepatoprotection, and skin protective effects. In addition, the novel preparations, new pharmacological effects,and cdusafty of liquiritin are also discussed in this review. CONCLUSION: This review provides a comprehensive state of knowledge on the pharmacokinetics and pharmacological activities of liquiritin, and makes a forecast for its research directions and applications in clinic.

Chemistry, pharmacokinetics, pharmacological activities, and toxicity of Quercitrin.

Quercitrin is a naturally available type of flavonoid that commonly functions as the dietary ingredient and supplement. So far, a wide spectrum of bioactivities of quercitrin have been revealed, including antioxidative stress, antiinflammation, anti-microorganisms, immunomodulation, analgesia, wound healing, and vasodilation. Based on these various pharmacological activities, increasing studies have focused on the potency of quercitrin in diverse diseases in recent years, such as bone metabolic diseases, gastrointestinal diseases, cardiovascular and cerebrovascular diseases, and others. In this paper, by collecting and summarizing publications from the recent years, the natural sources, pharmacological activities and roles in various diseases, pharmacokinetics, structure-activity relationship, as well as the toxicity of quercitrin were systematically reviewed. In addition, the underlying molecular mechanisms of quercitrin in treating related diseases, the dose-effect relationships, and the novel preparations were discussed on the purpose of broadening the application prospect of quercitrin as functional food and providing reference for its clinical application. Notably, clinical studies of quercitrin are insufficient at present, further high-quality studies are needed to firmly establish the clinical efficacy of quercitrin.

Protective effect of the combination of essential oil from patchouli and tangerine peel against gastric ulcer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

Geranium wilfordii maxim.: A review of its traditional uses, phytochemistry, pharmacology, quality control and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Geranium wilfordii Maxim. (family Geraniaceae) has been used as a multifunctional ethnomedicine in China for more than 600 years. There have been records about the edible and medicinal use of G.wilfordii since the Ming Dynasty. Nowadays, G.wilfordii is included in Chinese Pharmacopoeia as the Geranii Herba, and has been widely used to treat rheumatism, infectious diseases, dermatosis and tumors. In addition, more than 30 kinds of Chinese patent medicines containing G.wilfordii have been marketed in China for its high medicinal value. AIM OF THE REVIEW: The present review systematically summarized the traditional uses, phytochemistry, pharmacology, quality control and toxicology of G.wilfordii, discussed the development potential of this plant and analyzed the shortcomings of existing research, in order to provide comprehensive scientific basis for the medical application and help interested researchers discover safe and medicinal natural products from G.wilfordii. MATERIALS AND METHODS: We performed a systematic search of G.wilfordii by collecting the publications between 1995 and 2021 via PubMed, Web of Science, SciFinder, Google Scholar, Chinese National Knowledge Infrastructure database, Wanfang database and other databases using the keywords including Geranium wilfordii Maxim., botany, traditional uses, Chinese patent medicines, patents, preparations, phytochemistry, biological activity, quality and toxicity. Besides, part of the information also came from Chinese botanical and medical monographs. RESULTS: So far, more than 90 components have been identified from G.wilfordii, among which tannins as well as flavonoids have attracted widespread concerns. Due to the multi-components nature, a wide range of beneficial biological activities of G.wilfordii have been demonstrated, including anti-inflammatory, antibacterial, antiviral, anti-tumor, antioxidative, hepatoprotective, gastrointestinal protective, immunoregulatory and uric acid-lowering effects. CONCLUSION: A long history of traditional uses and abundant pharmacochemical and pharmacological studies have shown that G.wilfordii is an important natural medicine, which exerts outstanding therapeutic effects especially in anti-inflammation and anti-microorganisms. However, the present researches on the active ingredients and the mechanism of action are not in-depth enough, and more evidence-based scientific studies are needed to lend credence to the traditional uses of G.wilfordii. Additionally, limited toxicology tests cannot objectively evaluate the safety of G.wilfordii, which needs to be further supplemented. Further, more attention needs to be paid to the selection of index components of quality control research.

The chromosome-scale genome of Magnolia officinalis provides insight into the evolutionary position of magnoliids.

Magnolia officinalis, a representative tall aromatic tree of the Magnoliaceae family, is a medicinal plant that is widely used in diverse industries from medicine to cosmetics. We report a chromosome-scale draft genome of M. officinalis, in which ∼99.66% of the sequences were anchored onto 19 chromosomes with the scaffold N50 of 76.62 Mb. We found that a high proportion of repetitive sequences was a common feature of three Magnoliaceae with known genomic data. Magnoliids were a sister clade to eudicots-monocots, which provided more support for understanding the phylogenetic position among angiosperms. An ancient duplication event occurred in the genome of M. officinalis and was shared with Lauraceae. Based on RNA-seq analysis, we identified several key enzyme-coding gene families associated with the biosynthesis of lignans in the genome. The construction of the M. officinalis genome sequence will serve as a reference for further studies of Magnolia, as well as other Magnoliaceae.

Update on Pharmacological Activities, Security, and Pharmacokinetics of Rhein.

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein.

Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo.

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.

Water-soluble alkaloids extracted from Aconiti Radix lateralis praeparata protect against chronic heart failure in rats via a calcium signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies have shown the beneficial effects of aconite water-soluble alkaloid extract (AWA) in experimental models of heart disease, which have been ascribed to the presence of aconine, hypaconine, talatisamine, fuziline, neoline, and songorine. This study evaluated the effects of a chemically characterized AWA by chemical content, evaluated its effects in suprarenal abdominal aortic coarctation surgery (AAC)-induced chronic heart failure (CHF) in rats, and revealed the underlying mechanisms of action by proteomics. METHODS: Rats were distributed into different groups: sham, model, and AWA-treated groups (10, 20, and 40 mg/kg/day). Sham rats received surgery without AAC, whereas model rats an AWA-treated groups underwent AAC surgery. after 8 weeks, the treatment group was fed AWA for 4 weeks, and body weight was assessed weekly. At the end of the treatment, heart function was tested by echocardiography. AAC-induced chronic heart failure, including myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, was evaluated in heart tissue and plasma by RT-qPCR, ELISA, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TUNEL staining, and immunofluorescence staining of α-SMA, Col Ⅰ, and Col Ⅲ. Then, a proteomics approach was used to explore the underlying mechanisms of action of AWA in chronic heart failure. RESULTS: AWA administration reduced body weight gain, myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, and rats showed improvement in cardiac function compared to model group. The extract significantly ameliorated the AAC-induced altered expression of heart failure markers such as ANP, NT-proBNP, and ß-MHC, as well as fibrosis, hypertrophy markers MMP-2 and MMP-9, and other heart failure-related factors including plasma levels of TNF-α and IL-6. Furthermore, the extract reduced the protein expression of α-SMA, Col Ⅰ, and Col Ⅲ in the left ventricular (LV), thus inhibiting the LV remodeling associated with CHF. In addition, proteomics characterization of differentially expressed proteins showed that AWA administration inhibited left ventricular remodeling in CHF rats via a calcium signaling pathway, and reversed the expression of RyR2 and SERCA2a. CONCLUSIONS: AWA extract exerts beneficial effects in an AAC-induced CHF model in rats, which was associated with an improvement in LV function, hypertrophy, fibrosis, and apoptotic status. These effects may be related to the regulation of calcium signaling by the altered expression of RyR2 and SERCA2a.

Effects of allelochemical extracted from water lettuce (Pistia stratiotes Linn.) on the growth, microcystin production and release of Microcystis aeruginosa.

This study explored the optimisation of a method of extracting allelochemicals from Pistia stratiotes Linn., identified the optimal dose range for the allelochemicals' anti-algal effect and investigated their impact on the growth of Microcystis aeruginosa, as well as the production and release of microcystin-LR (MC-LR). Based on measured changes in algal cell density and chlorophyll a (Chl-a) content, the allelochemicals were confirmed to have the strongest anti-algal effect with the lowest half-effect concentration of 65 mg L(-1) when they were extracted using ethyl acetate as the extraction solvent, 1:20 g mL(-1) as the extraction ratio and 1 h as the extraction time. The allelochemicals extracted from P. stratiotes using this optimal method exhibited the strongest inhibitory effect on the growth of algae when used within a dose range of 60-100 mg L(-1); the relative inhibitory ratio reached 50-90%, and Chl-a content reduced 50-75% in algae cell cultures within 3-7 days. In addition, the extracted allelochemical compounds demonstrated no significant impact on the extracellular release of MC-LR during the culturing period. The amount of intracellular MC-LR per 10(6) algal cells increased depending on the increasing dose of allelochemicals from P. stratiotes after 7 days of culturing and maintained stability after 16 days. There was no increase in the total amount of MC-LR in the algal cell culture medium. Therefore, the application of allelochemicals from P. stratiotes to inhibit M. aeruginosa has a high degree of ecological safety and can be adopted in practical applications for treating water subjected to algae blooms because the treatment can effectively inhibit the proliferation of algal cells without increasing the release of cyanotoxin.