Glioblastoma stem cell-specific histamine secretion drives pro-angiogenic tumor microenvironment remodeling.

The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment. This histamine-producing ability is attributed to H3K4me3 modification-activated histidine decarboxylase (HDC) transcription via MYC. Notably, HDC is highly expressed in GBM, which is associated with poor survival of these patients. GSC-secreted histamine activates endothelial cells by triggering a histamine H1 receptor (H1R)-Ca2+-NF-κB axis, thereby promoting angiogenesis and GBM progression. Importantly, pharmacological blockage of H1R using antihistamines impedes the growth of GBM xenografts in mice. Our findings establish that GSC-specific metabolite secretion remodels the tumor microenvironment and highlight histamine targeting as a potential strategy for GBM therapy.

LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

An adolescent rat model of vincristine-induced peripheral neuropathy.

Childhood acute lymphoblastic leukemia (ALL) is a significant clinical problem that can be effectively treated with vincristine, a vinca alkaloid-based chemotherapeutic agent. However, nearly all children receiving vincristine treatment develop vincristine-induced peripheral neuropathy (VIPN). The impact of adolescent vincristine treatment across the lifespan remains poorly understood. We, consequently, developed an adolescent rodent model of VIPN which can be utilized to study possible long term consequences of vincristine treatment in the developing rat. We also evaluated the therapeutic efficacy of voluntary exercise and potential impact of obesity as a genetic risk factor in this model on the development and maintenance of VIPN. Out of all the dosing regimens we evaluated, the most potent VIPN was produced by fifteen consecutive daily intraperitoneal (i.p.) vincristine injections at 100 µg/kg/day, throughout the critical period of adolescence from postnatal day 35 to 49. With this treatment, vincristine-treated animals developed hypersensitivity to mechanical and cold stimulation of the plantar hind paw surface, which outlasted the period of vincristine treatment and resolved within two weeks following the cessation of vincristine injection. By contrast, impairment in grip strength gain was delayed by vincristine treatment, emerging shortly following the termination of vincristine dosing, and persisted into early adulthood without diminishing. Interestingly, voluntary wheel running exercise prevented the development of vincristine-induced hypersensitivities to mechanical and cold stimulation. However, Zucker fa/fa obese animals did not exhibit higher risk of developing VIPN compared to lean rats. Our studies identify sensory and motor impairments produced by vincristine in adolescent animals and support the therapeutic efficacy of voluntary exercise for suppressing VIPN in developing rats.

G3BP1 Inhibition Alleviates Intracellular Nucleic Acid-Induced Autoimmune Responses.

The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi-Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid-stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.

Hsa Circ 001839 Promoted Inflammation in Renal Ischemia-Reperfusion Injury Through NLRP3 by miR-432-3p.

BACKGROUND: In recent years, increasing discovery of the extremely important regulatory effects of circular RNAs on biological development, angiogenesis, tumor genesis, and development, as well as stem cell proliferation and differentiation has provided new opportunities for investigating regulation mechanism in angiogenesis. OBJECTIVES: This study explored the expression of circ 001839 in renal ischemia-reperfusion injury (RI-RI) rats and whether its upstream microRNA-432-3p (miR-432-3p) affects inflammation in both RI-RI rats and NRK52E cells. METHODS: Rat model of RI-RI was made, and circ 001839 was identified by the gene-chip analysis in RI-RI rats. Expression of circ 001839 and miR-432-3p was measured by reverse transcription-quantitative polymerase chain reaction, protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, interferon (IFN)-γ, IL-6, and IL-18 in rat serum and cell supernatant was determined by ELISA, and the expression of NOD-like receptor 3 (NLRP3) and other gap-associated proteins in NRK52E cells was evaluated by Western blot analysis. Next, to verify the regulatory relationship between circ 001839 and miR-432-3p, 2 luciferase reporters were constructed. RESULTS: Circ 001839 expression of RI-RI rats and NRK52E cells was significantly upregulated, compared with the control group. Circ 001839 overexpression significantly increased inflammation through promoting TNF-α, IFN-γ, and IL-6 expression levels in NRK52E cells. Overexpression of miR-432-3p significantly promoted inflammation in NRK52E cells via induction of NLRP3. Moreover, miR-432-3p decreased the effects of circ 001839-induced inflammation in NRK52E cells. CONCLUSIONS: These findings suggested that circ 001839 promoted inflammation in RI-RI through NLRP3 by miR-432-3p.

GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein.

Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, NR203K/G204R exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.

CEP55 promotes cilia disassembly through stabilizing Aurora A kinase.

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55-/- mice display clinical manifestations of Meckel-Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55-/- mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel-Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

Naturally-derived diterpenoid sphaeropsidin C as an activator of Nrf2/ARE pathway and its potential capability of relieving intracellular oxidative stress in human lung epithelial cells.

Oxidative stress is closely associated to the onset and progression of many human diseases. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway using naturally-derived molecules is an efficient strategy for alleviating the intracellular oxidative insults, and thus blocking the pathogenesis of oxidative stress-induced diseases. In the present study, a naturally-derived isopimarane-type diterpenoid sphaeropsidin C (SC) was identified to be an activator of Nrf2/ARE signaling pathway. Our data indicated that SC was able to stimulate Nrf2-mediated defensive system through promoting Nrf2 translocation, inhibiting Nrf2 ubiquitination, and enhancing Nrf2 stability in normal human lung epithelial Beas-2B cells. Furthermore, SC-induced Nrf2 activation required the involvement of protein kinases, exemplified by protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). It alleviated sodium arsenite [As(III)]-induced intracellular oxidative stress in an Nrf2-dependent manner. These results suggested that SC displayed potential application for the prevention and therapy against oxidative stress-induced diseases. Moreover, isopimarane-type diterpenoid represents a promising skeleton for developing Nrf2 activators.

CYP3A4 and microRNA-122 are involved in the apoptosis of HepG2 cells induced by ILs 1-decyl-3-methylimidazolium bromide.

Ionic liquids (ILs) as green alternatives for volatile organic solvents are increasingly used in commercial applications. It is necessary to explore the cytotoxic mechanism of ILs to reduce the risk to human health. For this purpose, cell viability, apoptosis, cytochrome P450 3A4 (CYP3A4), glucose transporter type 2 (GLUT2), and microRNA-122 (miR-122) gene expression in HepG2 cells was evaluated after IL exposure. The results showed that ILs reduced the viability of HepG2 cells through apoptotic cell death. Moreover, ILs markedly upregulated the transcription and protein levels of CYP3A4, but did not affect the expression of GLUT2 in either messenger RNA level or protein level. Finally, ILs increased the expression of miR-122 and inhibition of miR-122 with miR-122 inhibitor blocked ILs-induced apoptosis in HepG2 cells. This finding may contribute to an increased understanding of the in vitro molecular toxicity mechanism of ILs to further understand IL-related human health risks.

Botrysphin D attenuates arsenic-induced oxidative stress in human lung epithelial cells via activating Nrf2/ARE signaling pathways.

Oxidative stress is one of the main pathogenesis for many human diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays a key role in regulating intracellular antioxidant responses, and thus activation of Nrf2/ARE signaling pathway is a potential chemopreventive or therapeutic strategy to treat diseases caused by oxidative damage. In the present study, we have found that treatment of Beas-2B cells with botrysphins D (BD) attenuated sodium arsenite [As (III)]-induced cell death and apoptosis. Meanwhile, BD was able to upregulate protein levels of Nrf2 and its downstream genes NQO1 and γ-GCS through inducing Nrf2 nuclear translocation, enhancing protein stability, and inhibiting ubiquitination. It was also found that BD-induced activation of the Nrf2/ARE pathway was regulated by PI3K, MEK1/2, PKC, and PERK kinases. Collectively, BD is a novel activator of Nrf2/ARE pathway, and is verified to be a potential preventive agent against oxidative stress-induced damage in human lung tissues.

Novel diterpenoid-type activators of the Keap1/Nrf2/ARE signaling pathway and their regulation of redox homeostasis.

Oxidative stress is involved in the onset and progression of many human diseases. Activators of the Keap1/Nrf2/ARE pathway effectively inhibit the progression of oxidative stress-induced diseases. Herein, a small library of diterpenoids was established by means of phytochemical isolation, and chemical modification on naturally occurring molecules. The diterpenoids were subjected to a NAD(P)H: quinone reductase (QR) assay to evaluate its potential inhibition against oxidative stress. Sixteen diterpenoids were found to be novel potential activators of Nrf2-mediated defensive response. Of which, an isopimarane-type diterpenoid, sphaeropsidin A (SA), was identified as a potent activator of the Keap1/Nrf2/ARE pathway, and displayed approximately 5-folds potency than that of sulforaphane (SF). SA activated Nrf2 and its downstream cytoprotective genes through enhancing the stabilization of Nrf2 in a process involving PI3K, PKC, and PERK, as well as potentially interrupting Nrf2-Keap1 protein-protein interaction. In addition, SA conferred protection against sodium arsenite [As(III)]- and cigarette smoke extract (CSE)-induced redox imbalance and cytotoxicity in human lung epithelial cells, as wells as inhibited metronidazole (MTZ)-induced oxidative insult in Tg (krt4: NTR-hKikGR)cy17 transgenic zebrafish and lipopolysaccharide (LPS)-induced oxidative damage in wild-type AB zebrafish. These results imply that SA is a lead compound for therapeutic agent against oxidative stress-induced diseases, and diterpenoid is a good resource for discovering drug candidates and leads of antioxidant therapy.

AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression.

The capacity of cells to alter bioenergetics in response to the demands of various biological processes is essential for normal physiology. The coordination of energy sensing and production with highly energy-demanding cellular processes, such as cell division, is poorly understood. Here, we show that a cell cycle-dependent mitochondrial Ca2+ transient connects energy sensing to mitochondrial activity for mitotic progression. The mitochondrial Ca2+ uniporter (MCU) mediates a rapid mitochondrial Ca2+ transient during mitosis. Inhibition of mitochondrial Ca2+ transients via MCU depletion causes spindle checkpoint-dependent mitotic delay. Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). Our results establish a critical role for AMPK- and MCU-dependent mitochondrial Ca2+ signalling in mitosis and reveal a mechanism of mitochondrial metabolic adaptation to acute cellular energy stress.

Lignan and flavonoid support the prevention of cinnamon against oxidative stress related diseases.

BACKGROUND: Oxidative stress contributes to the pathogenesis of many human diseases. Cinnamon is a worldwide used spice, dietary supplement and traditional medicine, and is used for the therapy of oxidative stress related diseases. A well-established concept is that the functions of cinnamon preventing oxidative stress-induced diseases are attributed to the occurrence of cinnamaldehyde and its analogues. HYPOTHESIS: In our continuous searching of natural molecules with antioxidant capacity, we have found that cinnamaldehyde and its analogues in cinnamon are weak inhibitors of oxidative stress, and thus we speculate that there are novel and/or potent molecules inhibiting oxidative stress in cinnamon. STUDY DESIGN AND METHODS: A systemic phytochemical investigation of cinnamon using column chromatography was performed to identify the chemical constituents of cinnamon, and then their capacity of inhibiting oxidative stress and action of mechanism targeting Nrf2 pathway were investigated using diverse bioassay, including NAD(P)H: quinone reductase (QR) assay, immunoblot analysis, luciferase reporter gene assay, immunofluorescence and flow cytometry. RESULTS: Cinnamon improved the intracellular antioxidant capacity. A systemic phytochemical investigation of cinnamon gave the isolation of twenty-two chemical ingredients. The purified constituents were tested for their potential inhibitory effects against oxidative stress. Besides cinnamaldehyde analogues, a lignan pinoresinol (PRO) and a flavonol (-)-(2R,3R)-5,7-dimethoxy-3', 4'-methylenedioxy-flavan-3-ol (MFO) were firstly identified to be inhibitors of oxidative stress. Further study indicated that PRO and MFO activated Nrf2-mediated antioxidant response, and protected human lung epithelial cells against sodium arsenite [As(III)]-induced oxidative insults. CONCLUSION: The lignan PRO and the flavonoid MFO are two novel Nrf2 activators protecting tissues against oxidative insults, and these two constituents support the application of cinnamon as an agent against oxidative stress related diseases.

Catecholic Isoquinolines from Portulaca oleracea and Their Anti-inflammatory and ß2-Adrenergic Receptor Agonist Activity.

Isoquinoline alkaloids possess a wide range of structural features and pharmaceutical activities and are promising drug candidates. Ten water-soluble catecholic isoquinolines were isolated from the medicinal plant Portulaca oleracea, including three new (1-3) and seven known compounds (4-10), along with the known catecholamines 11 and 12 and four other known compounds (13-16). A method of polyamide column chromatography using EtOAc-MeOH as the mobile phase was developed for the isolation of catecholic isoquinolines. Alkaloids 1-12 exhibited anti-inflammatory activities (EC50 = 18.0-497.7 µM) through inhibition of NO production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among these compounds, 11, 2, 5, 4, and 8 were more potent than was the positive control, 3,4-dihydroxybenzohydroxamic acid (EC50 = 82.4 µM), with EC50 values of 18.0, 18.1, 35.4, 36.3, and 58.7 µM, respectively. Additionally, at 100 µM, compounds 1-12 showed different degrees of ß2-adrenergic receptor (ß2-AR) agonist activity in the CHO-K1/GA15 cell line which stably expressed ß2-AR as detected by a calcium assay. The EC50 values of 2 and 10 were 5.1 µM and 87.9 nM, respectively.

Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. METHODS: A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. RESULTS: A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). CONCLUSIONS: Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

Identification of novel Nrf2 activators from Cinnamomum chartophyllum H.W. Li and their potential application of preventing oxidative insults in human lung epithelial cells.

Human lung tissue, directly exposed to the environmental oxidants and toxicants, is apt to be harmed to bring about acute or chronic oxidative insults. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents a central cellular defense mechanism, and is a target for developing agents against oxidative insult-induced human lung diseases. Our previous study found that the EtOH extract of Cinnamomum chartophyllum protected human bronchial epithelial cells against oxidative insults via Nrf2 activation. In this study, a systemic phytochemical investigation of the aerial parts of C. chartophyllum led to the isolation of thirty chemical constituents, which were further evaluated for their Nrf2 inducing potential using NAD(P)H: quinone reductase (QR) assay. Among these purified constituents, a sesquiterpenoid bearing α, ß-unsaturated ketone group, 3S-(+)-9-oxonerolidol (NLD), and a diphenyl sharing phenolic groups, 3, 3', 4, 4'-tetrahydroxydiphenyl (THD) significantly activated Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO-1), and γ-glutamyl cysteine synthetase (γ-GCS), and enhanced the nuclear translocation and stabilization of Nrf2 in human lung epithelial cells. Importantly, NLD and THD had no toxicities under the Nrf2 inducing doses. THD also demonstrated a potential of interrupting Nrf2-Keap1 protein-protein interaction (PPI). Furthermore, NLD and THD protected human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. Taken together, we conclude that NLD and THD are two novel Nrf2 activators with potential application of preventing acute and chronic oxidative insults in human lung tissue.

Inflammatory Changes in Paravertebral Sympathetic Ganglia in Two Rat Pain Models.

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability (but not spontaneous activity) measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.

Physalis alkekengi L. var. franchetii (Mast.) Makino: An ethnomedical, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: The calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino (Physalis Calyx seu Fructus), have been widely used in traditional and indigenous Chinese medicines for the therapy of cough, excessive phlegm, pharyngitis, sore throat, dysuria, pemphigus, eczema, and jaundice with a long history. AIM OF THE REVIEW: The present review aims to achieve a comprehensive and up-to-date investigation in ethnomedical uses, phytochemistry, pharmacology, and toxicity of P. alkekengi var. franchetii, particularly its calyxes and fruits. Through analysis of these findings, evidences supporting their applications in ethnomedicines are illustrated. Possible perspectives and opportunities for the future research are analyzed to highlight the gaps in our knowledge that deserves further investigation. MATERIAL AND METHODS: Information on P. alkekengi var. franchetii was collected via electronic search of major scientific databases (e.g. Web of Science, SciFinder, Google Scholar, Pubmed, Elsevier, SpringerLink, Wiley online and China Knowledge Resource Integrated) for publications on this medicinal plant. Information was also obtained from local classic herbal literature on ethnopharmacology. RESULTS: About 124 chemical ingredients have been characterized from different parts of this plant. Steroids (particularly physalins) and flavonoids are the major characteristic and bioactive constituents. The crude extracts and the isolated compounds have demonstrated various in vitro and in vivo pharmacological functions, such as anti-inflammation, inhibition of tumor cell proliferation, antimicrobial activity, diuretic effect, anti-diabetes, anti-asthma, immunomodulation, and anti-oxidation. CONCLUSIONS: P. alkekengi var. franchetii is an important medicinal plant for the ethnomedical therapy of microbial infection, inflammation, and respiratory diseases (e.g. cough, excessive phlegm, pharyngitis). Phytochemical and pharmacological investigations of this plant definitely increased in the past half century. The chemical profiles, including ingredients and structures, have been adequately verified. Modern pharmacological studies supported its uses in the traditional and folk medicines, however, the molecular mechanisms of purified compounds remained unclear and were worth of further exploration. Therefore, the researchers should be paid more attention to a better utilization of this plant.