Arjunolic acid ameliorates lipopolysaccharide-induced depressive behavior by inhibiting neuroinflammation via microglial SIRT1/AMPK/Notch1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation is involved in the pathogenesis of depression disorder by activating microglia cells, increasing proinflammatory cytokines, effecting serotonin synthesis and metabolism, and neuronal apoptosis and neurogenesis. Arjunolic acid (ARG) is a triterpenoid derived from the fruits of Akebia trifoliata for treating psychiatric disorders in TCM clinic, which exhibits anti-inflammatory and neuroprotective effects. However, its anti-depressive effect and underlying mechanism are unknown. AIM OF THE STUDY: The aim of this study is to explore the effect of arjunolic acid on depression and its possible mechanisms. METHODS: Intraperitoneal injection of LPS in mice and LPS stimulated-BV2 microglia were utilized to set up in vivo and in vitro models. Behavioral tests, H&E staining and ELISA were employed to evaluate the effect of arjunolic acid on depression. RT-qPCR, immunofluorescence, molecular docking and Western blot were performed to elucidate the molecular mechanisms. RESULTS: Arjunolic acid dramatically ameliorated depressive behavior in LPS-induced mice. The levels of BDNF and 5-HT in the hippocampus of the mice were increased, while the number of iNOS + IBA1+ cells in the brain were decreased and Arg1+IBA1+ positive cells were increased after arjunolic acid treatment. In addition, arjunolic acid promoted the polarization of BV2 microglia from M1 to M2 type. Notably, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking technologies identified SIRT1 as the target of arjunolic acid. Moreover, after SIRT1 inhibition by using EX-527, the effects of arjunolic acid on ameliorating LPS-induced depressive behavior in mice and promoting M2 Microglia polarization were blocked. In addition, arjunolic acid activated AMPK and decreased Notch1 expression, however, inhibition of AMPK, the effect of arjunolic acid on the downregulation of Notch1 expression were weaken. CONCLUSIONS: This study elucidates that arjunolic acid suppressed neuroinflammation through modulating the SIRT1/AMPK/Notch1 signaling pathway. Our study demonstrates that arjunolic acid might serve as a potiential anti-depressant.

Aloe polymeric acemannan inhibits the cytokine storm in mouse pneumonia models by modulating macrophage metabolism.

The cytokine storm is highly associated with inflammatory-type disease severity and patients' survival. Plant polysaccharides, the main natural phytomedicine source, have a great potential to be an effective drug to treat cytokine storm. Herein we found that a polymeric acemannan (ABPA1) isolated from Aloe Vera Barbadensis extract C (AVBEC) exerted prominent inhibitory effects on inflammation-induced cytokine storm. The results displayed that ABPA1 effectively suppressed LPS-induced proinflammatory cytokines release in vitro. Moreover, ABPA1 treatment alleviated the cytokine storm and tissue damage in LPS- and IAV-induced mouse pneumonia models, and altered the phenotypic balance of macrophages in lung tissues. Functionally, ABPA1 enhanced macrophage M2 polarization and phagocytosis in RAW264.7 cells and inhibited LPS-induced M1 polarization. Mechanistically, ABPA1 enhanced mitochondrial metabolism and OXPHOS through activated PI3K/Akt/GSK-3ß signalling pathway. Overall, our findings suggest that ABPA1 may modulate macrophage activation and mitochondrial metabolism by targeting PI3K/Akt/GSK-3ß signalling pathway, thereby alleviating cytokine storm and inflammation.

An acetylated mannan isolated from Aloe vera induce colorectal cancer cells apoptosis via mitochondrial pathway.

The anti-cancer effects of Aloe vera barbadensis extract C (AVBEC) have been demonstrated in a previous study. However, the specific functional ingredient and mechanism remain undefined. This study aimed to evaluate the function and associated mechanisms of purified polysaccharide (ABPA1) from AVBEC on colorectal cancer. Here, we identify that ABPA1 can induce colorectal cancer apoptosis. In vivo, ABPA1 significantly suppressed tumor growth in an orthotopic colon cancer model. Mechanistically, ABPA1 alters mitochondrial membrane permeability by promoting Bax translocation while causing cytochrome-c release, which initiates the caspase cascade reaction. Additionally, we found that ABPA1 exerted distinct impacts on the mitochondrial metabolism of colorectal cancer cells. Our study elucidated the mechanism by which the polysaccharide ABPA1 induces apoptosis in colorectal cancer cells through the regulation of Bax and cytochrome-c mediated mitochondrial pathway, indicating that ABPA1 may be developed as a mitochondrial-targeting anti-cancer drug.

Aloe vera gel extract: Safety evaluation for acute and chronic oral administration in Sprague-Dawley rats and anticancer activity in breast and lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm. f. is a typical traditional Chinese medicine (TCM) collected in the Pharmacopoeia of the People's Republic of China (version 2015). It has been traditionally used for the treatment of constipation, and its potential therapeutic activities have been widely evaluated, including anti-tumor, anti-inflammatory and immune regulatory effects. The wide application of Aloe vera in food and therapy has raised safety issues and there are multiple safety assessments with a diverse toxicity and adverse effects from clinics and animals. AIM OF THE STUDY: This study aimed to investigate the safety of Aloe vera barbadensis extract C (AVBEC) in rats and analyze its anticancer activity in cell lines. MATERIALS AND METHODS: We administrated AVBEC orally in an acute toxicity study and a 6-month chronic toxicity study to observe and confirm its safety in Sprague-Dawley (SD) rats. Additionally, we explored the cytotoxicity of AVBEC in cancer cells and non-cancer cells. We further investigated the anti-tumor activity of AVBEC, and in the meantime, probed the function of component from AVBEC. RESULTS: No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 44.8 g·kg-1 and 4.48 g·kg-1, respectively. In the chronic toxicity study, AVBEC did not cause organ toxicity, including crucial organ structure and chemical function, and peripheral and central immune system damage. Additionally, we found that AVBEC could induce cancer cell apoptosis with a relatively higher apoptotic ratio than in non-cancer cells by decreasing adenosine triphosphate (ATP) concentration and enhancing reactive oxygen species (ROS) production. We also identified components in AVBEC using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) and probed the function of malic acid. This demonstrated that under the same circumstances, malic acid induced cell necrosis in cancer cells and non-cancer cells, while AVBEC did not. CONCLUSIONS: These results reveal a novel mechanism of aloe gel extract in regulating cancer cell apoptosis via modulating the mitochondrial metabolism and imply a possible application of AVBEC for the treatment of malignant cancer with the safety evaluation from rats and anticancer investigation from cancer cells and non-cancer cells.

A new polyhydroxylated oleanane triterpenoid from the roots of Rhodomyrtus tomentosa.

A new oleanane triterpenoid, 2α,3ß,6ß,23,29-pentahydroxyolean-12-en-28- oic acid (1), was isolated from the roots of Rhodomyrtus tomentosa, together with four known oleanane triterpenoids (2-5) and two known ursane triterpenoids (6-7). The structure of compound 1 was determined by extensive NMR and HR-ESI-MS data analysis. Compounds 4-5 showed cytotoxicity against PC12 cell lines at a concentration of 50 µM, and compound 1 exhibited moderate neuroprotective activity against corticosterone induced PC12 cell death at the same concentration.

Forsythiae Fructus: A Review on its Phytochemistry, Quality Control, Pharmacology and Pharmacokinetics.

Forsythiae Fructus, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved Forsythiae Fructus possesses various therapeutic effects, both in vitro and in vivo, such as anti-inflammatory, antibacterial and antiviral activities. Up to now, three hundred and twenty-one compounds have been identified and sensitive analytical methods have been established for its quality control. Recently, the pharmacokinetics of Forsythiae Fructus and its bioactive compounds have been reported, providing valuable information for its clinical application. Therefore, this systematic review focused on the newest scientific reports on Forsythiae Fructus and extensively summarizes its phytochemistry, pharmacology, pharmacokinetics and standardization procedures, especially the difference between the two applied types-unripe Forsythiae Fructus and ripe Forsythiae Fructus-in the hope of providing a helpful reference and guide for its clinical applications and further studies.

The Hedyotis diffusa Willd. (Rubiaceae): A Review on Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics.

Hedyotis diffusa Willd (H. diffusa) is a well-known Chinese medicine with a variety of activities, especially its anti-cancer effect in the clinic. Up to now, 171 compounds have been reported from H. diffusa, including 32 iridoids, 26 flavonoids, 24 anthraquinones, 26 phenolics and their derivatives, 50 volatile oils and 13 miscellaneous compounds. In vitro and in vivo studies show these phytochemicals and plant extracts to exhibit a range of pharmacological activities of anti-cancer, antioxidant, anti-inflammatory, anti-fibroblast, immunomodulatory and neuroprotective effects. Although a series of methods have been established for the quality control of H. diffusa, a feasible and reliable approach is still needed in consideration of its botanical origin, collecting time and bioactive effects. Meanwhile, more pharmacokinetics researches are needed to illustrate the characteristics of H. diffusa in vivo. The present review aims to provide up-to-date and comprehensive information on the phytochemistry, pharmacology, quality control and pharmacokinetic characteristics of H. diffusa for its clinical use and further development.

Association analysis between 12 genetic variants of ten genes and personality traits in a young chinese Han population.

Some genes involved in neurotransmission synthesis and transmission have been hypothesized to affect personality traits. To investigate the possible roles of these genes in personality traits of 16 Personality Factor Questionnaire, we performed a population-based study in a young Chinese Han cohort. In the study, we selected some functional variations in ten candidate genes (COMT, DBH, DRD(2), DRD(3), DAT, MAOA, GRM(1), GRIN2B, 5-TH(2A), and 5-TH(6)) encoding components in dopamine, glutamate, and 5-hydroxytryptamine pathways. The results showed the T102C in 5-TH(2A) was associated with X3 (emotional and quiet alertness) and B (reasoning) (F = 4.71 and 6.23; p = 0.009 and 0.002), Val158Met in COMT with E (dominance) (F = 7.01; p = 0.0009), while the variations in DBH, DRD(2), DRD(3), MAOA, GRM(1), GRIN2B, and 5-TH(6) were not associated with any of the personality traits. This finding suggests that T102C in 5-TH(2A) and Val158Met in COMT play roles in some human personality traits.