The molecular mechanism of polysaccharides in combating major depressive disorder: A comprehensive review.

Major depressive disorder (MDD) is a complex psychiatric condition with diverse etiological factors. Typical pathological features include decreased cerebral cortex, subcortical structures, and grey matter volumes, as well as monoamine transmitter dysregulation. Although medications exist to treat MDD, unmet needs persist due to limited efficacy, induced side effects, and relapse upon drug withdrawal. Polysaccharides offer promising new therapies for MDD, demonstrating antidepressant effects with minimal side effects and multiple targets. These include neurotransmitter, neurotrophin, neuroinflammation, hypothalamic-pituitary-adrenal axis, mitochondrial function, oxidative stress, and intestinal flora regulation. This review explores the latest advancements in understanding the pharmacological actions and mechanisms of polysaccharides in treating major depression. We discuss the impact of polysaccharides' diverse structures and properties on their pharmacological actions, aiming to inspire new research directions and facilitate the discovery of novel anti-depressive drugs.

A review of the botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality of Anemarrhena asphodeloides Bunge.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of Anemarrhena asphodeloides Bunge., belonging to the family Liliaceae, are named 'Zhi-mu' according to traditional Chinese medicine theory. It is a medicinal plant that has long been used as a tonic agent in various ethnomedicinal systems in East Asia, especially in China, and also for treating arthralgia, hematochezia, tidal fever, night sweats, cough, dry mouth and tongue, hemoptysis, etc. THE ARM OF THE REVIEW: The review aims to provide a systematic overview of botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides and to explore the future therapeutic potential and scientific potential of this plant. MATERIALS AND METHODS: A comprehensive literature search was performed on Anemarrhena asphodeloides using scientific databases including Web of Science, PubMed, Google Scholar, CNKI, Elsevier, SpringerLink, ACS publications, ancient books, Doctoral and master's Theses. Collected data from different sources was comprehensively summarised for botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides. RESULTS: A comprehensive analysis of the literature as mentioned above confirmed that the ethnomedical uses of Anemarrhena asphodeloides had a history of thousands of years in eastern Asian countries. Two hundred sixty-nine compounds have been identified from Anemarrhena asphodeloides, including steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, polysaccharides, benzophenones and other ingredients. Studies have shown that the extracts and compounds from Anemarrhena asphodeloides have extensive pharmacological activities, such as nervous system activity, antitumour, anti-inflammatory, antidiabetic, antiosteoporotic, antiallergic, antiplatelet aggregation, antimicrobial, antiviral, anti-ageing, hair growth promoting, preventing cell damage, etc. Evaluating the quality and toxicity of Anemarrhena asphodeloides is essential to confirm its safe use in humans. CONCLUSION: Anemarrhena asphodeloides is widely used in traditional medicine and have diverse chemical constituents with obvious biological activities. Nevertheless, more studies should be carried out in animals and humans to evaluate the cellular and molecular mechanisms involved in its biological activity and confirm its safe use.

A review on the advances in the extraction methods and structure elucidation of Poria cocos polysaccharide and its pharmacological activities and drug carrier applications.

Poria cocos polysaccharide (PCP) is one of the main active components of Poria cocos that is extensively used in the world. PCP can be divided into intro-polysaccharides and exopolysaccharides. PCP is mainly composed of glucose, galactose and mannose. There are many methods to exact PCP, and methods can affect its yield. PCP and its derivatives exhibit diverse biological functions such as antitumour, antioxidant, anti-inflammatory, immune-regulatory, hepatoprotective, etc. There is the potential application of PCP as drug carriers. The review provides a comprehensive summary of the latest extraction and purification methods of PCP, its chemistry, synthesis of PCP derivates, their pharmacological activities and their applications as drug carriers. This review provides comprehensive information on PCP, which can be used as the basis for further research on PCP and its derivates.

Unveiling Mechanism of Organic Photogenerator for Hydroxyl Radicals Generation by Molecular Modulation.

Photodynamic therapy (PDT) with organic photosensitizers generally goes through the oxygen-dependent process, generating singlet oxygen and/or superoxide anion. However, the generation of reactive oxygen species is often suppressed as a result of hypoxia, one of the common features in tumors, therefore limiting the effectiveness of the tumor treatments. Consequently, it is urgent and significant to develop an oxygen-independent hydroxyl radical photogenerator and unveil the mechanism. In this work, a hydroxyl radical (·OH) photogenerator originating from the electron transfer process is engineered. Detailed mechanism studies reveal that the optimized photosensitizer, WS2D, which contains a bithiophene unit, could both promote charge carrier generation and accelerate reaction efficiency, resulting in the efficient production of ·OH. In addition, WS2D nanoparticles are constructed to improve the polydispersity and stability in aqueous solution, which exhibit excellent biocompatibility and mitochondrial targeting. Bearing the above advantages, WS2D is employed in phototheranostics, which could release ·OH effectively and damage mitochondria precisely, achieving high PDT efficiency in vitro and in vivo. Overall, this work successfully provides valuable insights into the structural design of a hydroxyl radicals (·OH) photogenerator with great practical perspectives.

Effect of Pheretima aspergillum on reducing fibrosis: A systematic review and meta-analysis.

Background: Pheretima aspergillum (common name: Earthworm, Chinese name: dilong) has been used in traditional Chinese medicine for thousands of years. Recently, a few scientific studies have investigated the antifibrotic effects of Dilong extract (DE) and produced controversial results. We conducted a meta-analysis to make an informed decision on the antifibrotic effects of Dilong extract. Methods: The studies on antifibrotic effects of Dilong extract published until July 2022 in the scientific databases [PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, SinoMed and WanFang database] were reviewed. The RevMan 5.4.1 software was used for standardized mean difference (SMD) analysis. Two researchers independently reviewed all the studies, and their quality was assessed using the Cochrane risk of bias tool. Results: A total of 325 studies were found in the scientific databases; however, only 13 studies met the criteria for analysis. Dilong extract treatment was associated with antifibrotic effects via inhibiting the transforming growth factor beta 1 (TGF-ß1, SMD = -3.16, 95% CI: -4.18, -2.14, p < .00001) and alpha-smooth muscle actin (α-SMA: SMD = -2.57, 95% CI: -3.47, -1.66, p < .00001). Conclusion: Dilong extract effectively reduces tissue fibrosis; thus, further scientific studies should be conducted to investigate and develop it for clinical use. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022357141.

Real-time imaging mitochondrial viscosity dynamic during mitophagy mediated by photodynamic therapy.

Photodynamic therapy has been generally developed and approved as a promising theranostic technique in recent years, which requires photosensitizers to bear high efficiency of reactive oxygen species production, precisely targeting ability and excellent biocompatibility. The real-time monitoring the microenvironments such as viscosity dynamic involved in mitophagy mediated by photodynamic therapy is significantly important to understand therapeutic process but barely reported. In this work, a pyridinium-functionalized triphenylamine derivative, (E)-4-(2-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)vinyl)-1-methylpyridin-1-ium iodide (Mito-I), was exploited as photosensitizer for mitochondria-targeted photodynamic therapy and as fluorescent probe for imaging the mitochondrial viscosity dynamic during mitophagy simultaneously. The results indicated that the additional phenyl ring in Mito-I was beneficial to promote its efficiency of singlet oxygen production. The excellent capability of targeting mitochondria and singlet oxygen generation allowed Mito-I for the specifically mitochondria-targeted photodynamic therapy. Moreover, Mito-I displayed off-on fluorescence response to viscosity with high selectivity and sensitivity. The observed enhancement in fluorescence intensity of Mito-I revealed the increasingly mitochondrial viscosity during mitophagy mediated by the photodynamic therapy of Mito-I. As a result, this work presents a rare example to realize the mitochondria-targeting photodynamic therapy as well as the real-time monitoring viscosity dynamic during mitophagy, which is of great importance for the basic medical research involved in photodynamic therapy.

Defective transition metal hydroxide-based nanoagents with hypoxia relief for photothermal-enhanced photodynamic therapy.

Recently, phototherapy has attracted much attention due to its negligible invasiveness, insignificant toxicity and excellent applicability. The construction of a newly proposed nanosystem with synergistic photothermal and photodynamic tumor-eliminating properties requires a delicate structure design. In this work, a novel therapeutic nanoplatform (denoted as BCS-Ce6) based on defective cobalt hydroxide nanosheets was developed, which realized hypoxia-relieved photothermal-enhanced photodynamic therapy against cancer. Defective cobalt hydroxide exhibited high photothermal conversion efficacy at the near-infrared region (49.49% at 808 nm) as well as enhanced catalase-like activity to produce oxygen and greatly boost the singlet oxygen generation by a photosensitizer, Ce6, realizing efficacious dual-modal phototherapy. In vivo and in vitro experiments revealed that BCS-Ce6 can almost completely extinguish implanted tumors in a mouse model and present satisfactory biocompatibility during the treatment. This work sets a new angle of preparing photothermal agents and constructing comprehensive therapeutic nanosystems with the ability to modulate the hypoxic tumor microenvironment for efficient cancer therapy.

Lamellar Metal Oxide Based Nanoagent Realizing Intensive Interlamellar Ca2+ Release and Hypoxia Relief for Enhanced Synergistic Therapy.

As an emerging cancer treatment, Ca2+-loaded nanoagents can disorder intracellular calcium homeostasis to induce cancer cell death. However, the developed Ca2+ nanocarriers are very limited in variety. Herein, we developed a metal oxide based nanoagent, Ca0.35CoO2@ss-SiO2-Ce6 (denoted as CCO@ss-SiO2-Ce6), which not only intensively released Ca2+ but also realized enhanced photothermal and photodynamic therapy. The excellent photothermal conversion efficacy (48.01% at 808 nm laser illumination, 1 W/cm2), high heat-enhanced release rate of Ca2+ (50.09% at pH 4.5), and catalase-mimic activity to generate oxygen as well as the facilitated production of the singlet oxygen all contributed to the enhanced synergistic cancer therapy efficacy. The in vitro and in vivo experiments displayed that CCO@ss-SiO2-Ce6 demonstrated superior biocompatibility and remarkable suppressive tumor growth. This work opens a pathway for fabricating synergistic therapeutic nanoplatforms.

In-Situ-Bloomed Micrometer-Scale Ultrathin Nanosheets in Tumor-Microenvironment for Intensive Photothermal-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT), as the emerging modality of cancer therapy based on Fenton or Fenton-like reactions, still suffers from low efficacy of hydroxyl radical generation, which requires full exposure of reaction sites of CDT nanoagents to intracellular H2O2. However, the amount of exposed reaction sites is severely restrained by the controlled size (<200 nm) and the limited specific surface area of nanoagents. Herein, we highlight the in-situ bloomed micrometer-scale CoMn-based layered double hydroxide (CoMn-LDH) ultrathin nanosheets, which are derived from CoMn boride-based CMB@ss-SF nanospheres in response to overexpressed glutathione (GSH) and dissolved oxygen in tumor microenvironment (TME), accomplishing intensive photothermal-enhanced CDT. The micrometer-scale CoMn-LDH ultrathin nanosheets would provide abundant reactive sites to accelerate heterogeneous Fenton-like reaction as well as GSH depletion, eliciting quick release of metal ions and further realizing intensive homogeneous Fenton-like reactions for ·OH generation. Moreover, the nanoagent can harvest 808 nm light into heat, which can be utilized to promote the CDT efficacy and realize photoacoustic imaging (PAI). Because of acidity and overexpressed GSH in TME, the nanoagent exhibited superior biodegradability. Benefiting from the synergistic advantages, CMB@ss-SF with negligible cytotoxicity completely eradicated the tumors in mouse. This work provides avenue for developing CDT nanoagents.

Defect-engineered transition metal hydroxide nanosheets realizing tumor-microenvironment-responsive multimodal-imaging-guided NIR-II photothermal therapy.

Exploiting two-dimensional nanomaterials as photo-based theranostic agents is promising for the highly efficient ablation of deep-tissue-buried tumors. However, they are limited by their poor absorption in the second near-infrared-light (NIR-II) bio-window (1000-1300 nm) and intrinsic nonbiodegradability. Herein, defect-rich sulfur-doped Ni(OH)2 (S-Ni(OH)2) nanosheets decorated with bovine serum albumin (BSA) as a novel theranostic agent is developed, which can accomplish multimodal-imaging-guided photothermal ablation of mouse cancers in the NIR-II bio-window. Sulfur doping extends the absorption spectra of Ni(OH)2 nanosheets from the visible to NIR-II bio-window, affording highly efficient photothermal conversion (58.20% for 1064 nm), entailing it to become an excellent contrast agent for photoacoustic imaging. Further, because of their intrinsic paramagnetic property, they can be applied for magnetic resonance imaging. Owing to the abundant defective sites in S-Ni(OH)2 nanosheets, they exhibit response to the tumor microenvironment, resulting in effective biodegradation and excretion from the body. In vivo toxicity experiments indicated that S-Ni(OH)2-BSA NSs delivered no appreciable toxicity and good biocompatibility. This work provides an avenue for the rational design of effective theranostics agents.

A NIR-I light-responsive superoxide radical generator with cancer cell membrane targeting ability for enhanced imaging-guided photodynamic therapy.

Photodynamic therapy (PDT), as an emerging treatment modality, which takes advantage of reactive oxygen species (ROS) generated upon light illumination to ablate tumours, has suffered from a limited treatment depth, strong oxygen dependence and short ROS lifespan. Herein, we developed a highly efficient NIR-I light (808 nm laser) initiated theranostic system based on a fluorescent photosensitizer (EBD-1) with cancer cell membrane targeting ability, which can realize large penetration depth in tissue, generate superoxide radicals (O2 -˙) to relieve the oxygen-dependence, confine the ROS oxidation at the cell membrane, and self-report the cell viability during the PDT process. In vivo experiments demonstrated that EBD-1 under 808 nm light successfully accomplished remarkable cancer ablation. This work will be beneficial for the design of novel photosensitizers for PDT-based theranostic systems.