scholarly journals Therapeutic potential of triptolide in autoimmune diseases and strategies to reduce its toxicity

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yaxin Cheng ◽  
Yonghua Zhao ◽  
Ying Zheng
Keyword(s):  
Autoimmune Diseases ◽  
Therapeutic Potential ◽  
Low Cost ◽  
Chinese Herb ◽  
Bioactive Compound ◽  
Redox Balance ◽  
Research Progress ◽  
Severe Toxicity ◽  
Tripterygium Wilfordii Hook F

AbstractWith the increasing epidemiology of autoimmune disease worldwide, there is an urgent need for effective drugs with low cost in clinical treatment. Triptolide, the most potent bioactive compound from traditional Chinese herb Tripterygium Wilfordii Hook F, possesses immunosuppression and anti-inflammatory activity. It is a potential drug for the treatment of various autoimmune diseases, but its clinical application is still restricted due to severe toxicity. In this review, the pharmacodynamic effects and pharmacological mechanisms of triptolide in autoimmune diseases are summarized. Triptolide exerts therapeutic effect by regulating the function of immune cells and the expression of cytokines through inflammatory signaling pathways, as well as maintaining redox balance and gut microbiota homeostasis. Meanwhile, the research progress on toxicity of triptolide to liver, kidney, reproductive system, heart, spleen, lung and gastrointestinal tract has been systematically reviewed. In vivo experiments on different animals and clinical trials demonstrate the dose- and time- dependent toxicity of triptolide through different administration routes. Furthermore, we focus on the strategies to reduce toxicity of triptolide, including chemical structural modification, novel drug delivery systems, and combination pharmacotherapy. This review aims to reveal the potential therapeutic prospect and limitations of triptolide in treating autoimmune diseases, thus providing guiding suggestions for further study and promoting its clinical translation.

scholarly journals Antigen-Specific Regulatory T Cell Therapy in Autoimmune Diseases and Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Claudia Selck ◽  
Margarita Dominguez-Villar
Keyword(s):  
Autoimmune Diseases ◽  
Treg Cell ◽  
Therapeutic Potential ◽  
Treg Cells ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Heterogenous Population ◽  
Clinical Trial Results

Regulatory T (Treg) cells are a heterogenous population of immunosuppressive T cells whose therapeutic potential for the treatment of autoimmune diseases and graft rejection is currently being explored. While clinical trial results thus far support the safety and efficacy of adoptive therapies using polyclonal Treg cells, some studies suggest that antigen-specific Treg cells are more potent in regulating and improving immune tolerance in a disease-specific manner. Hence, several approaches to generate and/or expand antigen-specific Treg cells in vitro or in vivo are currently under investigation. However, antigen-specific Treg cell therapies face additional challenges that require further consideration, including the identification of disease-relevant antigens as well as the in vivo stability and migratory behavior of Treg cells following transfer. In this review, we discuss these approaches and the potential limitations and describe prospective strategies to enhance the efficacy of antigen-specific Treg cell treatments in autoimmunity and transplantation.

Therapeutic potential of galectin-1 and galectin-3 in autoimmune diseases

2021 ◽  
Vol 27 ◽  
Author(s):  
Yi-Sheng He ◽  
Yu-Qian Hu ◽  
Kun Xiang ◽  
Yue Chen ◽  
Ya-Ting Feng ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Vital Role ◽  
Promising Therapeutic Target ◽  
Galectin 3

: Galectins are a highly conserved protein family that binds to β-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. It can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies indicate that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D) and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. These information may provide a novel and promising therapeutic target for autoimmune diseases.

scholarly journals Antidiabetic Activity ofGnidia glaucaandDioscorea bulbifera: Potent Amylase and Glucosidase Inhibitors

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Sougata Ghosh ◽  
Mehul Ahire ◽  
Sumersing Patil ◽  
Amit Jabgunde ◽  
Meenakshi Bhat Dusane ◽  
...  
Keyword(s):  
Petroleum Ether ◽  
Therapeutic Potential ◽  
Low Cost ◽  
Petroleum Ether Extract ◽  
Antidiabetic Activity ◽  
Biochemical Basis ◽  
Glucosidase Inhibitors ◽  
Treatment Of Diabetes

Diabetes is a metabolic disorder affecting about 220 million people worldwide. One of the most critical complications of diabetes is post-prandial hyper-glycemia (PPHG). Glucosidase inhibitor andα-amylase inhibitors are class of compounds that help in managing PPHG. Low-cost herbal treatment is recommended due to their lesser side effect for treatment of diabetes. Two plants with significant traditional therapeutic potential, namely,Gnidia glaucaandDioscorea bulbifera, were tested for their efficiency to inhibitα-amylase andα-glucosidase. Stem, leaf, and flower ofG. glaucaand bulb ofD. bulbiferawere sequentially extracted with petroleum ether, ethyl acetate, and methanol as well as separately with 70% ethanol. Petroleum ether extract of flower ofG. glaucawas found to inhibitα-amylase significantly (78.56%). Extracts were further tested against crude murine pancreatic, small intestinal, and liver glucosidase enzyme which revealed excellent inhibitory properties.α-glucosidase inhibition provided a strongin vitroevidence for confirmation of bothG. glaucaandD. bulbiferaas excellent antidiabetic remedy. This is the first report of its kind that provides a strong biochemical basis for management of type II diabetes usingG. glaucaandD. bulbifera. These results provide intense rationale for furtherin vivoand clinical study.

Treatment of Neurodegenerative Diseases with Bioactive Components ofTripterygium wilfordii

2019 ◽  
Vol 47 (04) ◽  
pp. 769-785 ◽  
Author(s):  
Jianheng Li ◽  
Jijun Hao
Keyword(s):  
Neurodegenerative Diseases ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Research Progress ◽  
Bioactive Components ◽  
Tripterygium Wilfordii Hook F ◽  
Autoimmune And Inflammatory Diseases ◽  
Tripterygium Wilfordii Hook

Tripterygium wilfordii Hook F. (TWHF), a traditional Chinese medicine, has been widely used to treat autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis in China. Recently, studies have demonstrated that the bioactive components of TWHF have effective therapeutic potential for neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis. In this paper, we summarize the research progress of triptolide and celastrol (the two major TWHF components) as well as their analogues in the treatment of neurodegenerative diseases. In addition, we review and discuss the molecular mechanisms and structure features of those two bioactive TWHF components, highlighting their therapeutic promise in neurodegenerative diseases.

scholarly journals Engineering IL-2 to Give New Life to T Cell Immunotherapy

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Willem W. Overwijk ◽  
Mary A. Tagliaferri ◽  
Jonathan Zalevsky
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Interleukin 2 ◽  
T Cell Subsets ◽  
Annual Review ◽  
High Dose ◽  
Publication Date ◽  
Severe Toxicity

Interleukin-2 (IL-2) is integral to immune system regulation. Its opposing immunostimulatory and immunosuppressive actions make it an attractive therapeutic target for cancer and autoimmune diseases. A challenge in developing IL-2-directed anticancer therapies has been how to stimulate effector T cells (Teffs) without inducing regulatory T cells (Tregs) in the tumor microenvironment; conversely, IL-2 therapy for autoimmune diseases requires Treg induction without further stimulation of Teffs. High-dose IL-2 is approved for melanoma and renal cell carcinoma, but its therapeutic value is limited by a need for frequent dosing at specialist centers, its short half-life, severe toxicity, and a lack of efficacy in most patients. Re-engineered IL-2 therapeutics are designed to have longer in vivo half-lives, target specific IL-2 receptor conformations to stimulate specific T cell subsets, or localize to target tissues to optimize efficacy and reduce toxicity. We discuss recent studies that elucidate the potential of newly engineered IL-2-based therapeutics for cancer and autoimmune diseases. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Jatrorrhizine Hydrochloride Suppresses RANKL-Induced Osteoclastogenesis and Protects against Wear Particle-Induced Osteolysis

2018 ◽  
Vol 19 (11) ◽  
pp. 3698 ◽  
Author(s):  
Hui Li ◽  
Jing Wang ◽  
Qiwen Sun ◽  
Gang Chen ◽  
Shengnan Sun ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Therapeutic Potential ◽  
Osteoclast Differentiation ◽  
Chinese Herb ◽  
Major Complication ◽  
Wear Particle ◽  
Osteoclast Formation ◽  
Marker Genes

Wear particle-induced aseptic prosthetic loosening is a major complication associated with total joint arthroplasty (TJA). A growing body of evidence suggests that receptor activator of nuclear factor κ-B ligand (RANKL)-stimulated osteoclastogenesis and bone resorption are responsible for peri-implant loosening. Thus, agents which attenuate excessive osteoclast differentiation and function have been considered to offer therapeutic potential for prolonging the life of TJA implants. Jatrorrhizine hydrochloride (JH), a major protoberberine alkaloid isolated from the traditional Chinese herb Coptis chinensis, has been reported to have antimicrobial, antitumor, and antihypercholesterolemic and neuroprotective activities. However, its effects on osteoclast biology remain unknown. Here, we found that JH inhibited RANKL-induced osteoclast formation and bone resorption in vitro and exerted protection against titanium (Ti) particle-induced osteolysis in vivo. Biochemical analysis demonstrated that JH suppressed RANKL-induced activation of MAPKs (p38 and ERK) which down-regulated the production of NFATc1 and NFATc1-regulated osteoclastic marker genes, such as TRAP, CTR and CTSK. Collectively, our findings suggest that JH may be a promising anti-osteoclastogenesis agent for treating periprosthetic osteolysis or other osteoclast-related osteolytic diseases.

scholarly journals Addressing MRSA infection and antibacterial resistance with peptoid polymers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiayang Xie ◽  
Min Zhou ◽  
Yuxin Qian ◽  
Zihao Cong ◽  
Sheng Chen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Low Cost ◽  
Infection Model ◽  
One Pot ◽  
Mrsa Infection ◽  
The One

AbstractMethicillin-Resistant Staphylococcus aureus (MRSA) induced infection calls for antibacterial agents that are not prone to antimicrobial resistance. We prepare protease-resistant peptoid polymers with variable C-terminal functional groups using a ring-opening polymerization of N-substituted N-carboxyanhydrides (NNCA), which can provide peptoid polymers easily from the one-pot synthesis. We study the optimal polymer that displays effective activity against MRSA planktonic and persister cells, effective eradication of highly antibiotic-resistant MRSA biofilms, and potent anti-infectious performance in vivo using the wound infection model, the mouse keratitis model, and the mouse peritonitis model. Peptoid polymers show insusceptibility to antimicrobial resistance, which is a prominent merit of these antimicrobial agents. The low cost, convenient synthesis and structure diversity of peptoid polymers, the superior antimicrobial performance and therapeutic potential in treating MRSA infection altogether imply great potential of peptoid polymers as promising antibacterial agents in treating MRSA infection and alleviating antibiotic resistance.

scholarly journals Therapeutic Potential and Immunomodulatory Role of Coenzyme Q10 and Its Analogues in Systemic Autoimmune Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 600
Author(s):  
Chary López-Pedrera ◽  
José Manuel Villalba ◽  
Alejandra Mª Patiño-Trives ◽  
Maria Luque-Tévar ◽  
Nuria Barbarroja ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Coenzyme Q10 ◽  
Lupus Erythematosus ◽  
Therapeutic Potential ◽  
Organ Damage ◽  
Experimental Models ◽  
Plasma Lipoproteins ◽  
Thrombotic Risk ◽  
Beneficial Effects

Coenzyme Q10 (CoQ10) is a mitochondrial electron carrier and a powerful lipophilic antioxidant located in membranes and plasma lipoproteins. CoQ10 is endogenously synthesized and obtained from the diet, which has raised interest in its therapeutic potential against pathologies related to mitochondrial dysfunction and enhanced oxidative stress. Novel formulations of solubilized CoQ10 and the stabilization of reduced CoQ10 (ubiquinol) have improved its bioavailability and efficacy. Synthetic analogues with increased solubility, such as idebenone, or accumulated selectively in mitochondria, such as MitoQ, have also demonstrated promising properties. CoQ10 has shown beneficial effects in autoimmune diseases. Leukocytes from antiphospholipid syndrome (APS) patients exhibit an oxidative perturbation closely related to the prothrombotic status. In vivo ubiquinol supplementation in APS modulated the overexpression of inflammatory and thrombotic risk-markers. Mitochondrial abnormalities also contribute to immune dysregulation and organ damage in systemic lupus erythematosus (SLE). Idebenone and MitoQ improved clinical and immunological features of lupus-like disease in mice. Clinical trials and experimental models have further demonstrated a therapeutic role for CoQ10 in Rheumatoid Arthritis, multiple sclerosis and type 1 diabetes. This review summarizes the effects of CoQ10 and its analogs in modulating processes involved in autoimmune disorders, highlighting the potential of these therapeutic approaches for patients with immune-mediated diseases.

A technique for protecting delicate specimens during processing

1989 ◽  
Vol 47 ◽  
pp. 982-983
Author(s):  
R.J. Mount ◽  
R.V. Harrison
Keyword(s):  
Basilar Membrane ◽  
Low Cost ◽  
Organ Of Corti ◽  
Region Of Interest ◽  
Sensory Epithelium ◽  
Physical Damage ◽  
Air Drying ◽  
Specimen Handling ◽  
Two Component

The sensory end organ of the ear, the organ of Corti, rests on a thin basilar membrane which lies between the bone of the central modiolus and the bony wall of the cochlea. In vivo, the organ of Corti is protected by the bony wall which totally surrounds it. In order to examine the sensory epithelium by scanning electron microscopy it is necessary to dissect away the protective bone and expose the region of interest (Fig. 1). This leaves the fragile organ of Corti susceptible to physical damage during subsequent handling. In our laboratory cochlear specimens, after dissection, are routinely prepared by the O-T- O-T-O technique, critical point dried and then lightly sputter coated with gold. This processing involves considerable specimen handling including several hours on a rotator during which the organ of Corti is at risk of being physically damaged. The following procedure uses low cost, readily available materials to hold the specimen during processing ,preventing physical damage while allowing an unhindered exchange of fluids.Following fixation, the cochlea is dehydrated to 70% ethanol then dissected under ethanol to prevent air drying. The holder is prepared by punching a hole in the flexible snap cap of a Wheaton vial with a paper hole punch. A small amount of two component epoxy putty is well mixed then pushed through the hole in the cap. The putty on the inner cap is formed into a “cup” to hold the specimen (Fig. 2), the putty on the outside is smoothed into a “button” to give good attachment even when the cap is flexed during handling (Fig. 3). The cap is submerged in the 70% ethanol, the bone at the base of the cochlea is seated into the cup and the sides of the cup squeezed with forceps to grip it (Fig.4). Several types of epoxy putty have been tried, most are either soluble in ethanol to some degree or do not set in ethanol. The only putty we find successful is “DUROtm MASTERMENDtm Epoxy Extra Strength Ribbon” (Loctite Corp., Cleveland, Ohio), this is a blue and yellow ribbon which is kneaded to form a green putty, it is available at many hardware stores.

Gene Silencing using siRNA for Preventing Liver Ischaemia-Reperfusion Injury

2018 ◽  
Vol 24 (23) ◽  
pp. 2692-2700 ◽  
Author(s):  
H. Susana Marinho ◽  
Paulo Marcelino ◽  
Helena Soares ◽  
Maria Luísa Corvo
Keyword(s):  
Gene Silencing ◽  
Reperfusion Injury ◽  
Therapeutic Potential ◽  
Major Complication ◽  
Ischaemia Reperfusion Injury ◽  
Small Interference Rna ◽  
Ischaemia Reperfusion ◽  
Promising Therapeutic Approach ◽  
Sirna Therapy

Background: Ischaemia-reperfusion injury (IRI), a major complication occurring during organ transplantation, involves an initial ischemia insult, due to loss of blood supply, followed by an inflammation-mediated reperfusion injury. A variety of molecular targets and pathways involved in liver IRI have been identified. Gene silencing through RNA interference (RNAi) by means of small interference RNA (siRNA) targeting mediators of IRI is a promising therapeutic approach. Objective: This study aims at reviewing the use of siRNAs as therapeutic agents to prevent IRI during liver transplantation. Method: We review the crucial choice of siRNA targets and the advantages and problems of the use of siRNAs. Results: We propose possible targets for siRNA therapy during liver IRI. Moreover, we discuss how drug delivery systems, namely liposomes, may improve siRNA therapy by increasing siRNA stability in vivo and avoiding siRNA off-target effects. Conclusion: siRNA therapeutic potential to preclude liver IRI can be improved by a better knowledge of what molecules to target and by using more efficient delivery strategies.

Sign in / Sign up

Export Citation Format

Share Document