Ameliorative effect of anisodamine (654-1/654-2) against myocardial dysfunction induced by septic shock via the NF-κB/NLRP-3 or the PI3K-AKT/NF-κB pathway.

BACKGROUND: Septic shock, an extremely dangerous condition that causes impairment of organ function, always largely contributes to mortality in intensive care units. The impact of septic shock-induced organ damage on morbidity and mortality is substantially influenced by myocardial dysfunction. However, it remains unclear whether and in what manner anisodamine (654-1/654-2) ameliorates myocardial dysfunction caused by septic shock. PURPOSE: This study is the pioneering investigation and validation about the protective efficacy of anisodamine (654-1/654-2) against LPS-induced myocardial dysfunction in septic shock rats. It also aims to explore the differences in the underlying molecular mechanisms of both drugs. METHODS: A septic shock model was established in SD rats by after tail vein administration of LPS. 64 rats were distributed into eight groups, such as LPS group, control group, LPS+654-1 group (1.25, 2.5, and 5 mg/kg), and LPS+654-2 group (1.25, 2.5, and 5 mg/kg). The hemodynamics, echocardiography, immunohistochemical analysis, TEM, TUNEL assay, and H&E staining were utilized to assess the septic shock model and myocardial function. Lactic acid, inflammatory markers (IL-1ß, IL-6, and TNF-α), endothelial injure markers (SDC-1, HS and TM) and myocardial injury markers (CK, c-TNT and NT-pro BNP) were assessed using ELISA or biochemical kits. Additionally, the mechanisms of 654-1/654-2 were analyzed using RNA-seq and bioinformatics, and validated using western blotting and RT-PCR. RESULTS: Administration of 654-1/654-2 significantly restored hemodynamics and improved myocardial and endothelial glycocalyx injury in septic shock rats. Furthermore, 654-1/654-2 dose-dependently reduced plasma levels of lactic acid, inflammatory cytokines, and markers of endothelial and myocardial injury. Analyses using RNA-seq, WB and RT-PCR techniques indicated that 654-1/654-2 could mitigate myocardial and endothelial injury by inhibiting the NF-κB and NLRP-3 pathways, and activating the PI3K-AKT pathway. CONCLUSIONS: These findings demonstrated that 654-1/654-2 could alleviate myocardial damage in septic shock rats. Specifically, 654-1 inhibited the NF-κB/NLRP-3 pathway, whereas 654-2 promoted the PI3K-AKT pathway and inhibited the NF-κB pathway, effectively mitigating the inflammatory response and cell apoptosis.

GC-MS Fingerprinting Combined with Chemical Pattern-Recognition Analysis Reveals Novel Chemical Markers of the Medicinal Seahorse.

Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang Dynasty. Hippocampus kelloggi (HK) is the most common seahorse species in the medicinal material market and is one of the genuine sources of medicinal seahorse documented in the Chinese pharmacopeia. It is mainly cultivated in the Shandong, Fujian, and Guangxi Provinces in China. However, pseudo-HK, represented by Hippocampus ingens (HI) due to its similar appearance and traits, is often found in the market, compromising the safety and efficacy of clinical use. Currently, there is a lack of reliable methods for identifying these species based on their chemical composition. In this study, we employed, for the first time, a strategy combining gas chromatography-mass spectrometry (GC-MS) fingerprints and chemical patterns in order to identify HK and HI; it is also the first metabolomic study to date of HI as to chemical components. The obtained results revealed remarkable similarities in the chemical fingerprints, while significant differences were also observed. By employing hierarchical cluster analysis (HCA) and principal component analysis (PCA), based on the relative contents of their characteristic peaks, all 34 samples were successfully differentiated according to their species of origin, with samples from the same species forming distinct clusters. Moreover, nonadecanoic acid and behenic acid were exclusively detected in HK samples, further distinguishing them from HI samples. Additionally, the relative contents of lauric acid, tetradecanoic acid, pentadecanoic acid, n-hexadecanoic acid, palmitoleic acid, margaric acid, oleic acid, fenozan acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) exhibited significant differences between HK and HI (p < 0.0001), as determined by an unpaired t-test. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified seven components (DHA, EPA, n-hexadecanoic acid, tetradecanoic acid, palmitoleic acid, octadecanoic acid, and margaric acid) with high discriminatory value (VIP value > 1). Thus, nonadecanoic acid, behenic acid, and these seven compounds can be utilized as chemical markers for distinguishing HK from HI. In conclusion, our study successfully developed a combined strategy of GC-MS fingerprinting and chemical pattern recognition for the identification of HK and HI, and we also discovered chemical markers that can directly differentiate between the two species. This study can provide a foundation for the authentication of Hippocampus and holds significant importance for the conservation of wild seahorse resources.

Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity.

Cardiometabolic multimorbidity (CMM) is an increasingly significant global public health concern. It encompasses the coexistence of multiple cardiometabolic diseases, including hypertension, stroke, heart disease, atherosclerosis, and T2DM. A crucial component to the development of CMM is the disruption of endothelial homeostasis. Therefore, therapies targeting endothelial cells through multi-targeted and multi-pathway approaches hold promise for preventing and treatment of CMM. Curcumin, a widely used dietary supplement derived from the golden spice Carcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1ß, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against CMM through the regulation of endothelial function. It is worth noting that there is a close relationship between the progression of CMM and endothelial damage, characterized by oxidative stress, inflammation, abnormal NO bioavailability and cell adhesion. This paper provides a comprehensive review of curcumin, including its availability, pharmacokinetics, pharmaceutics, and therapeutic application in treatment of CMM, as well as the challenges and future prospects for its clinical translation. In summary, curcumin shows promise as a potential treatment option for CMM, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of CMM.

Alpinia katsumadai Hayata Volatile Oil Is Effective in Treating 5-Fluorouracil-Induced Mucositis by Regulating Gut Microbiota and Modulating the GC/GR Pathway and the mPGES-1/PGE2/EP4 Pathways.

This study was aimed to investigate the therapeutic effect and mechanism of AKHO on 5-fluorouracil (5-FU)-induced intestinal mucositis in mice. Mouse body weight, diarrhea score, and H&E staining were applied to judge the therapeutic effect of AKHO. 16S rDNA and nontargeted metabolomics have been used to study the mechanism. WB, ELISA, and immunohistochemistry were adopted to validate possible mechanisms. The results demonstrated that AKHO significantly reduced diarrhea scores and intestinal damage induced by 5-FU in mice. AKHO lowered the serum levels of LD and DAO, and upregulated the expressions of ZO-1 and occludin in the ileum. Also, AKHO upregulated the abundance of Lactobacillus in the gut and suppressed KEGG pathways such as cortisol synthesis and secretion and arachidonic acid metabolism. Further validation studies indicated that AKHO downregulated the expressions of prostaglandin E2 (PGE2), microsomal prostaglandin E synthase-1 (mPGES-1), and PGE2 receptor EP4, as well as upregulated the expression of glucocorticoid (GC) receptor (GR), leading to improved intestinal epithelial barrier function. Taken together, AKHO elicited protective effects against 5-FU-induced mucositis by regulating the expressions of tight junction proteins via modulation of GC/GR and mPGES-1/PGE2/EP4 pathway, providing novel insights into the utilization and development of this pharmaceutical/food resource.

Therapeutic potential of toosendanin: Novel applications of an old ascaris repellent as a drug candidate.

Toosendanin (TSN), extracted from Melia. toosendan Sieb.et Zucc. and Melia. azedarach L., has been developed into an ascaris repellent in China. However, with the improvement of public health protection, the incidence of ascariasis has been reduced considerably, resulting in limited medical application of TSN. Therefore, it is questionable whether this old ascaris repellent can develop into a drug candidate. Modern studies have shown that TSN has strong pharmacological activities, including anti-tumor, anti-botulinum, anti-viral and anti-parasitic potentials. It also can regulate fat formation and improve inflammation. These researches indicate that TSN has great potential to be developed into a corresponding medical product. In order to better development and application of TSN, the availability, pharmacodynamics, pharmacokinetics and toxicology of TSN are summarized systematically. In addition, this review discusses shortcomings in the current researches and provides useful suggestions about how TSN developed into a drug candidate. Therefore, this paper illustrates the possibility of developing TSN as a medical product, aimed to provide directions for the clinical application and further research of TSN.

Novel wine in an old bottle: Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases.

Atherosclerotic cardiovascular disease (ASCVD) frequently results in sudden death and poses a serious threat to public health worldwide. The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets. Therefore, the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention. Andrographolide (AG) is a diterpenoid lactone compound extracted from Andrographis paniculata. In addition to its use in conditions such as sore throat, AG can be used to prevent and treat ASCVD. It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity, diabetes, hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis (AS) including lipid accumulation, inflammation, oxidative stress and cellular abnormalities by regulating various targets and pathways. However, the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated, which may hinder its clinical development and application. Therefore, this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD. The findings support the use of the old pharmacological compound ('old bottle') as a novel drug ('novel wine') for the prevention and treatment of ASCVD. Additionally, this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG, aiming to provide more information regarding the clinical application and further research and development of AG.

Ginsenoside Rb1 stabilized and paclitaxel / protopanaxadiol co-loaded nanoparticles for synergistic treatment of breast tumor.

Ginsenosides are the major and key components for ginseng to exert its wide and beneficial therapeutic efficacy in clinic. Meanwhile, many ginsenosides and their metabolites showed in vitro an in vivo anti-tumor activity, among which ginsenoside Rb1 has attracted much attention due to its good solubility and amphipathy. In this study, the self-assembly behavior of Rb1 was investigated and the Rb1 nano-assembly could further stabilize or encapsulated hydrophobic drugs such as protopanaxadiol (PPD) and paclitaxel (PTX) to form nanoparticles, based on which, a natural nanoscale drug delivery system, ginsenoside Rb1 stabilized and PTX/PPD co-loaded nanoparticles (GPP NPs) were prepared. The resultant GPP NPs exhibited a small particle size of 126.2 nm, a narrow size distribution (PDI=0.145), and a zeta potential of -27.3 mV. PTX loading content was 11.06% with an encapsulation efficiency of 93.86%. GPP NPs were spherical and stable in normal saline, 5% glucose, PBS, plasma, or on-shelf storage for 7 days. Both PTX and PPD existed in an amorphous state in GPP NPs and were released in a sustained pattern. GPP NPs showed 10-fold higher in vitro anti-tumor activity of than PTX injections. In the in vivo experiment, GPP NPs achieved a much higher tumor inhibition rate than PTX injections (64.95% vs 43.17%, P < 0.01) and certain tumor target ability. In conclusion, GPP NPs had significantly enhanced anti-tumor efficacy and improved tumor microenvironment, thus were promising to be developed into a novel anti-tumor agent for the treatment of breast tumor.

Geographic Differentiation of Essential Oil from Rhizome of Cultivated Atractylodes lancea by Using GC-MS and Chemical Pattern Recognition Analysis.

The rhizome of Atractylodes lancea (RAL) is a well-known Chinese herbal medicine (CHM) that has been applied in clinical settings for thousands of years. In the past two decades, cultivated RAL has gradually replaced wild RAL and become mainstream in clinical practice. The quality of CHM is significantly influenced by its geographical origin. To date, limited studies have compared the composition of cultivated RAL from different geographical origins. As essential oil is the primary active component of RAL, a strategy combining gas chromatography-mass spectrometry (GC-MS) and chemical pattern recognition was first applied to compare the essential oil of RAL (RALO) from different regions in China. Total ion chromatography (TIC) revealed that RALO from different origins had a similar composition; however, the relative content of the main compounds varied significantly. In addition, 26 samples obtained from various regions were divided into three categories by hierarchical cluster analysis (HCA) and principal component analysis (PCA). Combined with the geographical location and chemical composition analysis, the producing regions of RAL were classified into three areas. The main compounds of RALO vary depending on the production areas. Furthermore, a one-way analysis of variance (ANOVA) revealed that there were significant differences in six compounds, including modephene, caryophyllene, γ-elemene, atractylon, hinesol, and atractylodin, between the three areas. Hinesol, atractylon, and ß-eudesmol were selected as the potential markers for distinguishing different areas by orthogonal partial least squares discriminant analysis (OPLS-DA). In conclusion, by combining GC-MS with chemical pattern recognition analysis, this research has identified the chemical variations across various producing areas and developed an effective method for geographic origin tracking of cultivated RAL based on essential oils.

Mechanism of Magnolia Volatile Oil in the Treatment of Acute Pancreatitis Based on GC-MS, Network Pharmacology, and Molecular Docking.

Objective: Magnoliae officinalis cortex (MOC) is one of the most frequently used traditional Chinese medicine (TCM) for the treatment of acute pancreatitis (AP). Magnolia volatile oil (MVO) is considered to be one of the main active ingredients in MOC for AP treatment. However, the underlying mechanism of MVO in AP therapy is unknown. Methods: An integrated strategy of gas chromatography-mass spectrum (GC-MS), network pharmacology, and molecular docking simulation was employed to predict underlying mechanism of MVO in AP treatment. First, the compounds of MVO were identified by GC-MS, and the targets of the identified characteristic compounds were collected from several databases, as well as AP-related targets. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to obtain the mechanism. Moreover, the binding activity between core therapeutic targets and their corresponding compounds was evaluated by molecular docking simulation. Results: GC-MS results showed a total of 35 compounds that appeared in at least 18 out of 20 chromatograms were considered as characteristic compounds of MVO, and 33 compounds of those were identified. Network analysis demonstrated that 33 compounds regulated 142 AP-related targets. Of those, 8 compounds (α-eudesmol, γ-eudesmol, (-)-terpinen-4-ol, terpineol, hinesol, linalool, borneol, and ß-eudesmol) and 8 targets (TNF, IL-1ß, PPARγ, PPARα, PTGS2, NCOA1, CNR1, and ESR1) have a close relationship with AP treatment and were recognized as the key active compounds and the core therapeutic targets, respectively. The 142 targets were involved in both inflammation and calcium overload-related biological pathways, such as neuroactive ligand-receptor interaction, estrogen, MAPK, and calcium signaling pathway. Moreover, molecular docking simulation indicated that the 8 core therapeutic targets strongly interacted with their corresponding compounds. Conclusions: In summary, the present study elucidated that the efficacy of MVO in AP treatment might be attributed to anti-inflammation and inhibition of calcium overload through multicomponents and multitargets.

Therapeutic potential of dietary flavonoid hyperoside against non-communicable diseases: targeting underlying properties of diseases.

Non-communicable diseases (NCDs) are a global epidemic with diverse pathogenesis. Among them, oxidative stress and inflammation are the most fundamental co-morbid features. Therefore, multi-targets and multi-pathways therapies with significant anti-oxidant and anti-inflammatory activities are potential effective measures for preventing and treating NCDs. The flavonol glycoside compound hyperoside (Hyp) is widely found in a variety of fruits, vegetables, beverages, and medicinal plants and has various health benefits, especially excellent anti-oxidant and anti-inflammatory properties targeting nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. In this review, we summarize the pathogenesis associated with oxidative stress and inflammation in NCDs and the biological activity and therapeutic potential of Hyp. Our findings reveal that the anti-oxidant and anti-inflammatory activities regulated by Hyp are associated with numerous biological mechanisms, including positive regulation of mitochondrial function, apoptosis, autophagy, and higher-level biological damage activities. Hyp is thought to be beneficial against organ injuries, cancer, depression, diabetes, and osteoporosis, and is a potent anti-NCDs agent. Additionally, the sources, bioavailability, pharmacy, and safety of Hyp have been established, highlighting the potential to develop Hyp into dietary supplements and nutraceuticals.

Can aloin develop to medicines or healthcare products?

In folk medicine, Aloe, a genus of Aloaceae, is constantly developed into laxative drugs or products and skin remedies with tremendous popularity worldwide. However, almost all products of Aloe are in roughly processed form. Therefore, developing related products of the active ingredients derived from Aloe is of great medical value. Aloin is a quality standard compound based on the Chinese Pharmacopoeia (CHP). It has a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, anti-osteoporotic, organ-protective, anti-viral, anti-microbial, anti-parasitic, and laxative potentials. Moreover, it regulates blood lipids and glucose and improves neuropathic pain effects, depicting potential to be transformed into promising medicines and healthcare products. In addition to the functional cosmetics and health products of Aloe, the availability, pharmacological activities, pharmacokinetics, formulation studies, and toxicity of aloin were summarized after investigating the literature from PubMed, Google, and other databases. Moreover, significant attention had been paid to the development of aloin-derived medicines and healthcare products. Thus, the present review clarified the possibility of aloin as medicines and healthcare products to develop and utilize Aloe resources.

Comparison of Volatile Oil between the Ligusticum sinese Oliv. and Ligusticum jeholense Nakai et Kitag. Based on GC-MS and Chemical Pattern Recognition Analysis.

Ligustici Rhizoma et Radix (LReR) is the dried rhizomes and roots of Ligusticum sinese Oliv. (LS) or Ligusticum jeholense Nakai et Kitag. (LJ). However, in the market, LS and LJ are frequently confused with each other. Since the volatile oils are both the main active components and quality control indicators of LReR, a strategy combining gas chromatography-mass spectrometry (GC-MS) and chemical pattern recognition (CPR) was used to compare the volatile components of LJ and LS. Total ion chromatography (TIC) revealed that phthalides (i.e., neocnidilide) and phenylpropanoids (i.e., myristicin) could be thought of as the most critical components in the volatile oils of LJ and LS, respectively. In addition, the chemical components of the volatile oils in LJ and LS were successfully distinguished by hierarchical cluster analysis (HCA) and principal component analysis (PCA). Moreover, two quality markers, including myristicin and neocnidilide, with a very high discriminative value for the classification of LJ and LS, were found by orthogonal partial least squares discriminant analysis (OPLS-DA). The relative contents of myristicin and neocnidilide were 10.86 ± 6.18% and 26.43 ± 19.63% for LJ, and 47.43 ± 12.66% and 2.87 ± 2.31% for LS. In conclusion, this research has developed an effective approach to discriminating LJ and LS based on volatile oils by combining GC-MS with chemical pattern recognition analysis.

New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder in the elderly characterized by memory loss and cognitive dysfunction. The pathogenesis of AD is complex. One-targeted anti-AD drugs usually fail to delay AD progression. Traditional Chinese medicine records have documented the use of the roots of Panax ginseng (ginseng roots) and its prescriptions to treat dementia. Ginsenoside Rg1, the main ginsenoside component of ginseng roots, exhibits a certain therapeutic effect in the abovementioned diseases, suggesting its potential in the management of AD. Therefore, we combed the pathogenesis of AD and currently used anti-AD drugs, and reviewed the availability, pharmacokinetics, and pharmaceutic studies of ginsenoside Rg1. This review summarizes the therapeutic effects and mechanisms of ginsenoside Rg1 and its deglycosylated derivatives in AD in vivo and in vitro. The main mechanisms include improvement in Aß and Tau pathologies, regulation of synaptic function and intestinal microflora, and reduction of inflammation, oxidative stress, and apoptosis. The underlying mechanisms mainly involve the regulation of PKC, MAPK, PI3K/Akt, CDK5, GSK-3ß, BDNF/TrkB, PKA/CREB, FGF2/Akt, p21WAF1/CIP1, NF-κB, NLRP1, TLR3, and TLR4 signaling pathways. As the effects and underlying mechanisms of ginsenoside Rg1 on AD have not been systematically reviewed, we have provided a comprehensive review and shed light on the future directions in the utilization of ginsenoside Rg1 and ginseng roots as well as the development of anti-AD drugs.

Vasorelaxant Activities and its Underlying Mechanisms of Magnolia Volatile Oil on Rat Thoracic Aorta Based on Network Pharmacology.

Objective: Magnolia volatile oil (MVO) is a mixture mainly containing eudesmol and its isomers. This study was to investigate the vasorelaxant effects and the underlying mechanism of MVO in rat thoracic aortas. Method: The present study combined gas chromatography-mass spectrometry (GC-MS) and network pharmacology analysis with in vitro experiments to clarify the mechanisms of MVO against vessel contraction. A compound-target network, compound-target-disease network, protein-protein interaction network, compound-target-pathway network, gene ontology, and pathway enrichment for hypertension were applied to identify the potential active compounds, drug targets, and pathways. Additionally, the thoracic aortic rings with or without endothelium were prepared to explore the underlying mechanisms. The roles of the PI3K-Akt-NO pathways, neuroreceptors, K+ channels, and Ca2+ channels on the vasorelaxant effects of MVO were evaluated through the rat thoracic aortic rings. Results: A total of 29 compounds were found in MVO, which were identified by GC-MS, of which 21 compounds with a content of more than 0.1% were selected for further analysis. The network pharmacology research predicted that beta-caryophyllene, palmitic acid, and (+)-ß-selinene might act as the effective ingredients of MVO for the treatment of hypertension. Several hot targets, mainly involving TNF, CHRM1, ACE, IL10, PTGS2, REN, and F2, and pivotal pathways, such as the neuroactive ligand-receptor interaction, the calcium signaling pathway, and the PI3K-Akt signaling, were responsible for the vasorelaxant effect of MVO. As expected, MVO exerted a vasorelaxant effect on the aortic rings pre-contracted by KCl and phenylephrine in an endothelium-dependent and non-endothelium-dependent manner. Importantly, a pre-incubation with indomethacin (Indo), N-nitro-L-arginine methyl ester, methylene blue, wortmannin, and atropine sulfate as well as 4-aminopyridione diminished MVO-induced vasorelaxation, suggesting that the activation of the PI3K-Akt-NO pathway and KV channel were involved in the vasorelaxant effect of MVO, which was consistent with the results of the Kyoto Encyclopedia of Genes and the Genomes. Additionally, MVO could significantly inhibit Ca2+ influx resulting in the contraction of aortic rings, revealing that the inhibition of the calcium signaling pathway exactly participated in the vasorelaxant activity of MVO as predicted by network pharmacology. Conclusion: MVO might be a potent treatment of diseases with vascular dysfunction like hypertension. The underlying mechanisms were related to the PI3K-Akt-NO pathway, KV pathway, as well as Ca2+ channel, which were predicted by the network pharmacology and verified by the experiments in vitro. This study based on network pharmacology provided experimental support for the clinical application of MVO in the treatment of hypertension and afforded a novel research method to explore the activity and mechanism of traditional Chinese medicine.

Pro-Angiogenic Effects of Essential Oil from Perilla frutescens and Its Main Component (Perillaldehyde) on Zebrafish Embryos and Human Umbilical Vein Endothelial Cells.

PURPOSE: Perilla frutescens (L.) Britt., a traditional edible-medicinal herb in China, has been used to treat cardiovascular and cerebrovascular (cardio-cerebrovascular) diseases for thousands of years. However, knowledge of the mechanisms underlying the effects of essential oil from P. frutescens (EOPF) in the treatment of cardio-cerebrovascular diseases is lacking. The promotion of angiogenesis is beneficial in the treatment of ischemic cardio-cerebrovascular diseases. The current study investigated the pro-angiogenic role of EOPF and its main component perillaldehyde in sunitinib-injured transgenic Tg (flk1:EGFP) zebrafish embryos and human umbilical vein endothelial cells (HUVECs) for the first time. MATERIALS AND METHODS: The pro-angiogenic effects of EOPF and perillaldehyde were observed in vivo using transgenic Tg (flk1:EGFP) zebrafish embryos and in vitro using HUVECs. Cell viability, proliferation, migration, tube formation, and protein levels were detected by MTT, EdU staining, wound healing, transwell chamber, and Western blot assays, respectively. RESULTS: EOPF and perillaldehyde exerted a significant stimulatory effect on the formation of zebrafish intersegmental vessels (ISVs). Moreover, EOPF and perillaldehyde promoted proliferation, migration, and tube formation in sunitinib-treated HUVECs. Additionally, our findings uncovered that the pro-angiogenic effects of EOPF and perillaldehyde were mediated by increases in the expression ratios of p-ERK1/2 to ERK1/2 and Bcl-2 to Bax. CONCLUSION: The present study is the first report to provide clear evidence that EOPF and perillaldehyde promote angiogenesis by stimulating repair of sunitinib-injured ISVs in zebrafish embryos and promoting proliferation, migration, and tube formation in sunitinib-injured HUVECs. The underlying mechanisms are related to increased p-ERK1/2 to ERK1/2 and Bcl-2 to Bax expression ratios. EOPF and perillaldehyde may be used in the treatment of cardio-cerebrovascular diseases, which is consistent with the traditional application of P. frutescens.

Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects.

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Review of Natural Resources With Vasodilation: Traditional Medicinal Plants, Natural Products, and Their Mechanism and Clinical Efficacy.

For decades, chronic diseases including cardiovascular and cerebrovascular diseases (CCVDs) have plagued the world. Meanwhile, we have noticed a close association between CCVDs and vascular lesions, such as hypertension. More focus has been placed on TMPs and natural products with vasodilation and hypotension. TMPs with vasodilatory and hypotensive activities are mainly from Compositae, Lamiaceae, and Orchidaceae (such as V. amygdalina Del., T. procuinbens L., M. glomerata Spreng., K. galanga L., etc.) whereas natural products eliciting vasorelaxant potentials were primarily from flavonoids, phenolic acids and alkaloids (such as apigenin, puerarin, curcumin, sinomenine, etc.). Furthermore, the data analysis showed that the vasodilatory function of TMPs was mainly concerned with the activation of eNOS, while the natural products were primarily correlated with the blockage of calcium channel. Thus, TMPs will be used as alternative drugs and nutritional supplements, while natural products will be considered as potential therapies for CCVDs in the future. This study provides comprehensive and valuable references for the prevention and treatment of hypertension and CCVDs and sheds light on the further studies in this regard. However, since most studies are in vitro and preclinical, there is a need for more in-depth researches and clinical trials to understand the potential of these substances.

Aqueous extracts of Aconite promote thermogenesis in rats with hypothermia via regulating gut microbiota and bile acid metabolism.

BACKGROUND: Intermittent or prolonged exposure to severe cold stress disturbs energy homeostasis and can lead to hypothermia, heart failure, Alzheimer's disease, and so on. As the typical "hot" traditional Chinese medicine, Aconite has been widely used to treat cold-associated diseases for thousands of years, but its critical mechanisms for the promotion of thermogenesis are not fully resolved. Gut microbiota and its metabolites play a crucial role in maintaining energy homeostasis. Here, we investigated whether the aqueous extracts of Aconite (AA) can enhance thermogenesis through modulation of the composition and metabolism of gut microbiota in hypothermic rats. METHODS: The therapeutic effects of AA on body temperature, energy intake, and the histopathology of white adipose tissue and brown adipose tissue of hypothermic rats were assessed. Microbiota analysis based on 16 S rRNA and targeted metabolomics for bile acids (BAs) were used to evaluate the composition of gut microbiota and BAs pool. The antibiotic cocktail treatment was adopted to further confirm the relationship between the gut microbiota and the thermogenesis-promoting effects of AA. RESULTS: Our results showed a sharp drop in rectal temperature and body surface temperature in hypothermic rats. Administration of AA can significantly increase core body temperature, surface body temperature, energy intake, browning of white adipose tissue, and thermogenesis of brown adipose tissue. Importantly, these ameliorative effects of AA were accompanied by the shift of the disturbed composition of gut microbiota toward a healthier profile and the increased levels of BAs. In addition, the depletion of gut microbiota and the reduction of BAs caused by antibiotic cocktails reduced the thermogenesis-promoting effect of AA. CONCLUSIONS: Our results demonstrated that AA promoted thermogenesis in rats with hypothermia via regulating gut microbiota and BAs metabolism. Our findings can also provide a novel solution for the treatment of thermogenesis-associated diseases such as rheumatoid arthritis, obesity, and type 2 diabetes.

A comparative study on the in vitro and in vivo antitumor efficacy of icaritin and hydrous icaritin nanorods.

Icaritin (ICT) and hydrous icaritin (HICT) are two similar flavonoids compounds isolated from Epimedium Genus. This is the first comparative study on their in vitro and in vivo antitumor effects. Nanorods (NRs) were prepared for ICT and HICT by anti-solvent precipitation method using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) as a stabilizer. The prepared ICT-NRs and HICT-NRs had similar diameter (155.5 nm and 201.7 nm), high drug loading content (43.30 ± 0.22% and 41.08 ± 0.19%), excellent stability and a similar sustaining drug release manner. Nanorods improved the in vitro toxicity against 4 different cancer cells in contrast to free ICT or free HICT; however, no significant difference was observed in this regard between ICT-NRs and HICT NRs. In the in vivo study on the anticancer efficacy on MCF-7 and PLC/PRE/5 tumor-bearing mice model, HICR-NRs displayed certain advantage over ICT NRs with higher tumor inhibition rate.

Combination of c oxidase subunit I based deoxyribonucleic acid barcoding and HPLC techniques for the identification and quality evaluation of Pheretima aspergillum.

This study aimed to identify Pheretima aspergillum (Guang-Pheretima) and its adulterants using the cytochrome c oxidase subunit I based deoxyribonucleic acid barcoding technology, and further to evaluate their quality using an optimized high-performance liquid chromatography method. For deoxyribonucleic acid barcoding identification, the Kimura-2-Parameter model was used to analyze genetic distance, and phylogenetic neighbor-joining tree was constructed for species identification of 20 labeled Guang-Pheretima samples. A high-performance liquid chromatography method was developed for the simultaneous determination of seven nucleoside components for quality evaluation. Compared with the GenBank database, 10 samples were identified as real Guang-Pheretima (P. aspergillum), and the others as the adulterants-Metaphire magna. The maximum intraspecific genetic distances of c oxidase subunit I sequence for P. aspergillum were smaller than the minimum interspecific genetic distances between P. aspergillum and M. magna. Ten P. aspergillum and 10 M. magna samples were clearly clustered in the neighbor-joining tree. The contents of seven nucleosides components in P. aspergillum were significantly higher than that in its adulterant-M. magna. The incidence of adulterants for Guang-Pheretima was high (up to 50%) with an alarming quality. This study provided a powerful idea for the quality evaluation of other highly valuable plant- or animal-derived products for safety concerns to avoid misidentification.