Recent advances in natural polysaccharides-based controlled release nanosystems for anti-cancer phototherapy.

Phototherapy, which relies on light to trigger phototherapeutic agents (PAs) to generate cytotoxic reactive oxygen species or hyperthermia, has received much attention in cancer treatment. However, traditional PAs have shortcomings such as low water solubility, easy aggregation-induced fluorescence quenching and low target site accumulation efficiency, which severely limit clinical anticancer applications. Naturally derived polysaccharides have attracted great attention in the scientific community in nano-drug delivery systems (NDDS) due to their abundant resources, biocompatibility, targeting ability, bioactivity and so on, which is expected to assist PAs to play a synergistic effect. This article reviews the recent progress of polysaccharides in the field of cancer phototherapy, including the advantages of polysaccharides as nanocarrier materials to deliver PAs; the main mechanism for the preparation of PAs-loaded polysaccharides nanoformulation; construction of polysaccharides-based NDDS for delivery of PAs and its functional modification strategy, hoping to further improve the therapeutic effect of phototherapy against cancer.

Calcium pectinate and hyaluronic acid modified lactoferrin nanoparticles loaded rhein with dual-targeting for ulcerative colitis treatment.

Herein, dual-bioresponsive of Rhein (RH) in promoting colonic mucous damage repair and controlling inflammatory reactions were combined by the dual-targeting (intestinal epithelial cells and macrophages) oral nano delivery strategy for effective therapy of ulcerative colitis (UC). Briefly, two carbohydrates, calcium pectinate (CP) and hyaluronic acid (HA) were used to modify lactoferrin (LF) nanoparticles (NPs) to encapsulate RH (CP/HA/RH-NPs). CP layer make CP/HA/RH-NPs more stable and protect against the destructive effects of the gastrointestinal environment and then release HA/RH-NPs to colon lesion site. Cellular uptake evaluation confirmed that NPs could specifically target and enhance the uptake rate via LF and HA ligands. in vivo experiments revealed that CP/HA/RH-NPs significantly alleviated inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway and accelerated colonic healing. Importantly, with the help of CP, this study was the first to attempt for LF as a targeting nanomaterial in UC treatment and offers a promising food-based nanodrug in anti-UC.

Integrated serum pharmacochemistry and network pharmacological analysis used to explore possible anti-rheumatoid arthritis mechanisms of the Shentong-Zhuyu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong-Zhuyu decoction (STZYD) has been recognized by the Chinese National Administration of Traditional Chinese Medicine (TCM) as a classic TCM formula. Use of STZYD has shown a satisfactory clinical therapeutic outcome for rheumatoid arthritis (RA); despite this, its bioactive chemical composition and relevant mechanism(s) of this action have not been clearly elucidated. AIM OF THE STUDY: To explore the bioactive chemical composition of STZYD used for RA treatment and its possible mechanism(s) of action. MATERIALS AND METHODS: Serum pharmacochemistry mediated by the UPLC-Q-Exactive MS/MS method was employed to identify the absorbed phytochemical compounds in serum derived from STZYD, which were commonly considered as the potential bioactive compounds. And then, these components were used to construct a compound-target network for RA using a network pharmacology approach, to predict the possible biological targets of STZYD along with potential signaling pathways. Afterwards, we established a Complete Freund's adjuvant (CFA)-induced RA rat model, and observed the anti-RA effect of STZYD by a series of indexes, including foot swelling, ankle diameter, arthritis score, morphological and radiographic analysis, serum inflammatory factors, and histopathological analysis of synovial tissues. Particularly, the predicted pathway by the combination of serum pharmacochemistry and network pharmacology was further validated using RT-qPCR, Western blot, and immunohistochemical analyses in animal experiment. RESULTS: Totally, 38 compounds derived from STZYD have been identified by serum sample analysis. Based on it, 387 genes related to these identified compounds in STZYD and 3807 genes related to RA were collected by network pharmacology. Critically, KEGG analysis indicated that the PI3K/AKT signaling pathway was recommended as one of the main pathway related to anti-RA effect of STZYD. Experimentally, STZYD significantly alleviated CFA-induced arthritis without any visible side-effects. Compared to the RA model group without any treatment, the treatment of STZYD significantly reduced the expression of both mRNA and protein targets in the PI3K/AKT signaling pathway. Furthermore, this result was also corroborated by immunohistochemistry analysis. All these studies could effectively corroborate the predicted result as above, suggested that the feasibility of this integrated strategy. CONCLUSION: This study provided a useful strategy to identify bioactive compounds and the potential mechanisms for TCM formula by integrating serum pharmacochemistry and network pharmacology.

Anti-platelet aggregation of Panax notoginseng triol saponins by regulating GP1BA for ischemic stroke therapy.

BACKGROUND: Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) in China for more than 17 years due to its anti-platelet aggregation and neuro-protective effects, but its mechanism of action is not fully understand. In this study, anti-platelet aggregation-related protein analysis and computer simulations of drug-protein binding interactions were performed to explore the mechanism of the effects of PTS against ischemic stroke in an ischemia reperfusion model. METHODS: Three oral doses of PTS were administered in a model of middle cerebral artery occlusion (MCAO) in rats. Panax notoginseng total saponins (PNS) and a combination of PTS and aspirin were chosen for comparison. To evaluate therapeutic effects and explore possible mechanisms of anti-platelet aggregation, we measured cerebral infarct size and water content in brain tissue, histomorphological changes, expression of related factors (such as arachidonic acid metabolites) and platelet receptors in serum, as well as the binding affinity of PTS for platelet adhesion receptors. RESULTS: Compared with PNS, PTS showed a stronger and more potent anti-platelet aggregation effect in MCAO model rats. The combination of PTS and aspirin could reduce adverse gastrointestinal effects by regulating the TXA2/PGI2 ratio. We demonstrated for the first time that PTS was able to regulate Glycoprotein Ib-α (GP1BA) in a model animal. The binding of ginsenoside Rg1 and GP1BA could form a stable structure. Moreover, PTS could reduce von Willebrand factor (VWF)-mediated platelet adhesion to damaged vascular endothelium, and thus enhance the probability of anti-platelet aggregation and anti-thrombosis under pathological conditions. CONCLUSIONS: Our results showed that GP1BA was closely related to the anti-platelet aggregation action of PTS, which provided new scientific and molecular evidence for its clinical application.

The protective effects of triptolide on age-related bone loss in old male rats.

BACKGROUND: Previous studies have showed that triptolide have a critical role in inhibiting osteoclast formation, bone resorption and attenuating regional osteoporosis. However, the protective role of triptolide on age-related bone loss has not been investigated. In the study, we assessed the effect of triptolide supplementation on bone microstructure and bone remolding in old male rat lumbars. METHODS: Fifty-two 22-month-old male Sprague-Dawley rats were randomly assigned to either triptolide treatment group or control group. Triptolide (15 µg/kg/d) or normal saline was administered to the rats of assigned group for 8 weeks. Lumbar bone mineral density (BMD) and bone microstructure were analyzed by micro-CT. Fluorochrome labeling of the bones was performed to measure the mineral apposition rate (MAR) and bone formation rate (BFR). Osteoclast number was also measured by TRAP staining. Plasma level of osteocalcin and tartrate-resistant acid phosphatase 5b (Tracp 5b) was also analyzed. RESULTS: Micro-CT results revealed that triptolide-treated rats had significant higher BMD, bone volume over total volume (BV/TV), trabecular thickness (Tb.Th), bone trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) compared to the control group. Although fluorochrome labeling result showed no significant difference in MAR and BFR between the groups, triptolide decreased osteoclast number in vivo. In addition, a significant higher level of plasma Tracp 5b was observed in the triptolide-treated rats. Furthermore, triptolide also reduced the expression of receptor for activation of NF-κB ligand (RANKL) and increased osteoprotegerin (OPG) expression in the lumbars. CONCLUSION: These results suggested that triptolide had a protective effect on age-related bone loss at least in part by reducing osteoclast number in elder rats. Therefore, triptolide might be a feasible therapeutic approach for senile osteoporosis.

Pocahemiketals A and B, two new hemiketals with unprecedented sesquiterpenoid skeletons from Pogostemon cablin.

Pocahemiketals A and B (1 and 2), two novel hemiketal sesquiterpenoids with unprecedented skeletons, were isolated from the essential oil of the aerial parts of Pogostemon cablin. In addition to a bicyclo[3.2.1]-carbon core, 1 and 2 possessed a hemiketal α,ß-unsaturated-γ-lactone moiety. Their structures were determined by extensive spectroscopic analysis, electronic circular dichroism calculation, and single-crystal X-ray diffraction. Compound 2 exhibited significant vasorelaxant activity against phenylephrine-induced contraction of a rat aorta ring with the EC50 value of 16.32µM.

[Study on constituents of the aerial parts of Pogostemon cablin].

OBJECTIVE: To investigate the chemical constituents of the aerial parts of Pogostemon cablin. METHODS: The constituents were isolated by column chromatography over silica gel, Sephadex LH-20 and C8. Structures were identified by spectroscopic data analysis. RESULTS: Thirteen compounds were obtained and elucidated as patchouli alcohol (1), pogostone (2), friedelin (3), epifriedelinol (4), oleanolic acid (5), methyl oleanolate (6), 5alpha-stigmast-3,6-dione (7), stigmast-4-ene-3-one (8), beta-sitosterol (9), pachypodol (10), retusin (11), (-)-guaiacylglycerol (12) and dibutyl phthalate (13). CONCLUSION: Compounds 6, 7, 8, 12 and 13 are isolated from this genus for the first time.

[Comprehensive research and evaluation of chlorogenic acid allergy].

OBJECTIVE: The non-allergy of chlorogenic acid was demonstrated by the study result of allergy with different purity of chlorogenic acid and comprehensive analysis of literature. METHOD: The allergies of different samples, which contained the different purity of chlorogenic acid extracts, chlorogenic acid for injection, interior solution of dialysis, external solution of dialysis, post-term chlorogenic acid for injection and chlorogenic acid for injection with degradation, were validated with active systemic anaphylaxis and passive cutaneous anaphylaxis on rats and guinea pigs respectively. The range of molecular weight of macromolecular remains after dialysis were identified by LC-MS. RESULT: Allergic reactions were happened in dialysis isolated macromolecular substances, which were identified by LC-MS, and lower purity extracts (purity of chlorogenic acid < or = 40%), while the reactions were not happened in isolated micromolecular substances and high purity samples (purity of chlorogenic acid > or = 92%). CONCLUSION: Macromolecules in lower purity of chlorogenic acid extracts were relative closely to the allergen causing anaphylaxis, but not the chlorogenic acid, which was demonstrated according to the study result and analysis of literatures home and abroad.