NIR-IIb fluorescence antiangiogenesis copper nano-reaper for enhanced synergistic cancer therapy.

The formation of blood vessel system under a relatively higher Cu2+ ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.

A homologous-targeting cGAS-STING agonist multimodally activates dendritic cells for enhanced cancer immunotherapy.

Herein, we developed a doxorubicin (Dox)-loaded and 4T1 cancer cell membrane-modified hydrogenated manganese oxide nanoparticles (mHMnO-Dox) to elicit systemic antitumor immune responses. The results revealed that mHMnO-Dox actively recognized tumor cells and then effectively delivered Dox into the cells. Upon entering tumor cells, the mHMnO-Dox underwent rapid degradation and abundant release of Mn2+ and chemotherapeutic drugs. The released Mn2+ not only catalysed a Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also activated the cGAS-STING pathway to boost dendritic cell (DC) maturation. This process increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. In addition, the released Dox could contribute to a chemotherapeutic effect, while activating DC cells and subsequently intensifying immune responses through immunogenic cell death (ICD) of tumor cells. Consequently, the mHMnO-Dox suppressed the primary and distal tumor growth and inhibited tumor relapse and metastasis, as well as prolonged the lifespan of tumor-bearing mice. Thus, the mHMnO-Dox multimodally activated DC cells to demonstrate synergistic antitumor activity, which was mediated via the activation of the cGAS-STING signalling pathway to regulate tumor microenvironment, ICD-mediated immunotherapy and ROS-mediated CDT. These findings suggest the therapeutic potential of mHMnO-Dox in cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A cancer cell membrane-camouflaged hydrogenated mesoporous manganese oxide (mHMnO) has been developed as a cGAS-STING agonist and ICD inducer. The mHMnO effectively induced abundance of ROS production in cancer cells, which caused cancer cell death and then promoted DC maturation via tumour-associated antigen presentation. Meanwhile, the mHMnO significantly activated cGAS-STING pathway to facilitate DC maturation and cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment, which further enhanced tumour immune response. In addition, the combination of the mHMnO and Dox could synergistically promote tumour ICD and then multimodally induce DC maturation, achieving an enhanced CIT. Overall, this study provides a potential strategy to design novel immunologic adjuvant for enhanced CIT.

[Chemical constituents and pharmacological effects of Dictamni Cortex: a review].

Dictamni Cortex, the dried root bark of Dictamnus dasycarpus, has many chemical constituents, such as alkaloids, limonoids, flavonoids, sesquiterpenoids, glycosides, and steroids.It has the effects of anti-inflammation, anti-fungi, anti-arteriosclerosis, stopping bleeding, anti-cancer, neuroprotection, and antioxidation.The chemical constituents of Dictamni Cortex are the important material basis for its medicinal effects.This paper reviewed the chemical constituents and pharmacological activities of Dictamni Cortex and analyzed the research trend and present research progress on this medicinal, with a view to its further development and utilization.

Hyperoside: A review on its sources, biological activities, and molecular mechanisms.

Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam. Medical research has found that hyperoside possesses a broad spectrum of biological activities, including anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects. These pharmacological properties lay the foundation for its use in treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers. Hyperoside is obtained from the plants and chemical synthesis. This study aims to provide a comprehensive overview of hyperoside on its sources and biological activities to provide insights into its therapeutic potential, and to provide a basis for high-quality studies to determine the clinical efficacy of this compound.

Salvia plebeia R. Br. polysaccharides (SPP) against RSV (respiratory syncytial virus) infection: Antiviral effect and mechanisms of action.

OBJECTIVE: To investigate the antiviral effect of Salvia plebeia R. Br. polysaccharides (SPP) against RSV and underlying mechanisms. METHODS: SPP was extracted via alcohol-precipitation method and extract was separated into various fractions using ultrafiltration method. The polysaccharide content was determined using UV-Vis. Antiviral effect of SPP and fractions was measured using MTT method and Reed-Muench method. Sixty Balb/c mice were randomly divided into 6 groups, and received either Ribavirin or SPP. Their body weight and food intake were recorded every day throughout the experiment period. The lung index inhibition ratio and pulmonary virus titer were determined followed by the histological analysis of lungs. Furthermore, time-of-addition and effective stage analysis were carried out to determine the mechanism of action. The TLR-3 and TLR-4 levels in the lungs were determined using qRT-PCR. The levels of IFN-γ, IL-2 and TNF-α in serum were determined using ELISA. RESULTS: The SPP content is 4.396%. SPP has shown a good anti-RSV effect both in vitro (TI = 123.041) and in vivo models. The antiviral activity of fractions with molecular weight ≥ 10,000 is found to possess more potent antiviral activity than other fractions. SPP inhibits the RSV proliferation and reduces the lung lesions induced by RSV. The mechanism of action involves the inhibition of TLR-3 and TLR-4 in lungs, up-regulation of IFN-γ and IL-2, and down-regulation of TNF-α in serum. It is also shown to improve the body's immune function. CONCLUSION: SPP has a potential to treat diseases caused by RSV.

Brucea javanica: A review on anticancer of its pharmacological properties and clinical researches.

BACKGROUND: The dried fruits of Brucea javanica (L.) Merr (BJ) is being widely investigated, both in lab and in clinic, to explore its potential anticancer activity and molecular mechanism involved. PURPOSE: We appraised the available literature and suggested the future research directions to improve the medicinal value of BJ. METHOD: In this review, we have summarized the scientific findings from experimental and clinical studies regarding the anticancer activity and mechanisms. RESULTS: Numerous studies have reported that BJ exerts anticancer effect on various types of cancer lines through inhibiting cell proliferation, inducing apoptosis, inhibiting migration/invasion, inducing autophagy and restraining angiogenesis. Brucea javanica triggers the generation of reactive oxygen species (ROS), release of cytochrome C, activation of mitochondrial apoptosis pathway and regulation of a series of signal pathways and proteins related to cancer. The molecular mechanism involved are inhibiting the PI3K/Akt/mTOR, NF-κB and Nrf2-Notch1 pathways; up or down modulating the levels of p53, p62, p21, Bax, and Bcl-2 respectively, and inhibiting the expression of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Brucea javanica's efficacy in treating cancer patients either as a main or supportive treatment is also discussed in this review. CONCLUSION: This review will serve as a comprehensive resource of BJ's potential as anticancer agent and its molecular pathways. The analysis of the literature suggests that BJ can serve as a potential candidate for the treatment of cancer.

[Research progress on chemical constituents and pharmacological effects of Sedum sarmentosum].

Sedum sarmentosum is a traditional Chinese medicine with the clinical effects of clearing away heat and detoxification. It has the pharmacological effects of protecting liver, anti-tumor, anti-fibrosis, anti-oxidation, inhibiting lipid accumulation and immunosuppression. Because of its remarkable effect of reducing enzymes and protecting the liver, it is mainly used for the treatment of various types of hepatitis in clinical application. The flavonoids, megastigmanes, alkaloids, sterols, triterpenes and other chemical constituents in S. sarmentosum are the important material basis for its pharmacological action. In this paper, the research progress on the chemical constituents and pharmacological effects of S. sarmentosum were reviewed, and the research status and research direction of S. sarmentosum were analyzed, in order to provide a reference for its further rational development and application.

A review: Natural polysaccharides from medicinal plants and microorganisms and their anti-herpetic mechanism.

The infections caused by Herpes simplex viruses (HSV-1 and -2) are seriously endangering the health of all human beings. Once infected with these two viruses, it will cause life-long latency in the host, and the continuous recurrence of the infection will seriously affect the quality of life. Moreover, infections with HSV-1 and HSV-2 have been reported to make the body susceptible to other diseases, such as Alzheimer's disease and HIV. Thus, more attention should be paid to the development of novel anti-HSV drugs. Polysaccharides obtained from medicinal plants and microorganism (both land and sea) are reported to be promising anti-herpes substances. However, their antiviral mechanisms are complex and diverse, which includes direct inhibition of virus life cycle (Adsorption, penetration, genetic material and protein synthesis) and indirectly through improving the body's immunity. And each step of the research processes from extraction to structural analysis contributes to the result in terms of antiviral activity. Therefore, The complex mechanisms involved in the treatment of Herpes simplex infections makes development of new antiviral compounds is difficult. In this paper, the mechanisms of polysaccharides in the treatment of Herpes simplex infections, the research processes of polysaccharides and their potential clinical applications were reviewed.

Salvia plebeia R. Br. : an overview about its traditional uses, chemical constituents, pharmacology and modern applications.

Salvia plebeia R. Br. (SP), has been widely used in traditional Chinese medicine (TCM). It contains a number of chemical components and reported to possess a variety of pharmacological activities. SP is distributed in many countries such as China, Korea, Japan, Afghanistan and India. SP was first described in Compendium of Materia Medica in the Ming dynasty. The aim of this review is to compile all the information reported in the literature on SP. This review covers traditional uses, including 16 TCM classics and 21 traditional prescriptions; a total of 93 compounds from SP have been reported, including flavonoids, monoterpenoids, sesquiterpenoids, diterpenoids, triterpenes, phenolic acids etc; biological actives such as antioxidant, antimicrobial, hypoglycaemic, anti-inflammatory, analgesic, sedative, antiasthmatic, antiviral, antitumour, hepatoprotective effects etc. In addition, this paper also compiled the quality control studies and clinical applications. The future prospects and the existing problems of SP were also discussed. Overall, we believe this review will be a comprehensive record of SP for researchers to refer for carrying out for further research.

Research progress on chemical constituents and pharmacological effects of Salvia miltiorrhiza / 中草药

Salvia miltiorrhiza is a commonly used Chinese materia medica for promoting blood circulation and removing blood stasis. It has a wide range of pharmacological effects and is mainly used for the treatment of irregular menstruation, palpitation, insomnia and various cardiovascular diseases, particularly angina pectoris and myocardial infarction. The chemical constituents of S. miltiorrhiza are the important material basis for its pharmacological effects. This paper reviews the research progress of the chemical constituents and pharmacological effects of S. miltiorrhiza. The research status and research direction of S. miltiorrhiza are analysed, which will provide a reference for its further research and development.

Applications of new methods in extraction of flavonoids from Chinese materia medica / 中草药

Flavonoids are widely found in medicinal plants, which have important medical properties. Flavonoids were proved to have many pharmacological activities, such as anti-oxidation, antitumor, antimutation, anti-inflammatory, antibacterial and anti-aging. The extraction of flavonoids is the crucial link in their clinical applications. In recent years, many emerging Chinese medicine extraction methods have also been widely used in the extraction of flavonoids. This paper reviews the current application of new methods for flavonoid extraction, in order to provide references for the extraction, development and utilization of flavonoids. These new extraction methods include supercritical fluid extraction (SFE), ultrasonic assisted extraction (UAE), microwave assisted extraction (MAE), pressurized liquid extraction (PLE), pulsed electric field (PEF) assisted extraction, enzyme assisted extraction (EAE), green solvent extraction, steam explosion assisted extraction, dynamic high pressure microfluidization (DHPM) assisted extraction, etc.