ABSTRACT
Chronic kidney disease (CKD) is a widespread ailment that significantly impacts global health. It is characterized by high prevalence, poor prognosis, and substantial healthcare costs, making it a major public health concern. The current clinical treatments for CKD are not entirely satisfactory, leading to a high demand for alternative therapeutic options. Chinese herbal medicine, with its long history, diverse varieties, and proven efficacy, offers a promising avenue for exploration. One such Chinese herbal medicine, Dioscorea nipponica Makino (DNM), is frequently used to treat kidney diseases. In this review, we have compiled studies examining the mechanisms of action of DNM in the context of CKD, focusing on five primary areas: improvement of oxidative stress, inhibition of renal fibrosis, regulation of metabolism, reduction of inflammatory response, and regulation of autophagy.
ABSTRACT
Diabetic nephropathy (DN) is a kidney disorder secondary to diabetes and is one of the main diabetic microvascular complications. As the number of diabetic patients grows, DN has become the leading cause of chronic kidney disease in China. Unfortunately, no definitive cure currently exists for DN. Cornus officinalis (CO), frequently utilized in clinical settings for diabetes mellitus treatment, has proven vital in both preventing and treating DN. This article explores the pathogenesis of DN and how CO and its active compounds regulate glucose and lipid metabolism, exhibit anti-inflammatory properties, inhibit oxidative stress, regulate podocytes, and manage autophagy. The mechanism and role of and its active compounds in the treatment of DN are discussed.
ABSTRACT
Dioscin (DIS) is a natural compound derived from Chinese herbal medicine. In recent years, multiple studies have reported that DIS has immunoregulation, antifibrosis, antiinflammation, antiviral and antitumor effects. However, the mechanism by which DIS ameliorates renal fibrosis and inflammation remains to be elucidated. The aim of the present study was to investigate the role of DIS in renal fibrosis and inflammation and to explore its underlying mechanism. It used network pharmacology to predict the targets of DIS for the treatment of renal interstitial fibrosis. The present study was performed using unilateral ureteral obstruction mice and HK2 cells in vivo and in vitro. The mice were treated with different doses of DIS. Kidney tissues were collected for histopathology staining, western blotting, immunohistochemistry staining and reverse transcriptionquantitative (RTq) PCR. TGFß1 (2 ng/ml) was used to induce renal fibrosis in the cells. Then, cells were respectively treated with DIS (3.125, 6.25, 12.5 µM) and Bay117082 (an inhibitor of NFκB p65 nuclear transcription, 1 µM) for another 24 h. The expressions of inflammatory factors and NFκB pathway proteins were detected by immunofluorescence, ELISA, western blotting and RTqPCR. DIS alleviated renal injury in the UUO mice. Mechanistically, DIS not only decreased the expressions of inflammatory factors including IL1ß, NODlike receptor thermal protein domain associated protein 3, monocyte chemotactic protein 1, IL6, TNFα and IL18 but also reduced the level of phosphorylation of NFκB p65 in vivo and in vitro, which was similar to the impact of Bay117082. DIS ameliorated renal fibrosis by inhibiting the NFκB signaling pathwaymediated inflammatory response, which may be a therapeutic pathway for delaying chronic kidney disease.
Subject(s)
Kidney Diseases , Ureteral Obstruction , Mice , Animals , NF-kappa B/metabolism , Kidney Diseases/drug therapy , Kidney Diseases/etiology , Kidney Diseases/metabolism , Kidney/pathology , Signal Transduction , Ureteral Obstruction/complications , Ureteral Obstruction/drug therapy , Ureteral Obstruction/metabolism , Inflammation/metabolism , FibrosisABSTRACT
Lipid deposition is an etiology of renal damage caused by lipid metabolism disorder in diabetic nephropathy (DN). Thus, reducing lipid deposition is a feasible strategy for the treatment of DN. Morroniside (MOR), an iridoid glycoside isolated from the Chinese herb Cornus officinalis Sieb. et Zucc., is considered to be an effective drug in inhibiting oxidative stress, reducing inflammatory response, and countering apoptosis. To explore the protective mechanism of MOR in attenuating renal lipotoxicity in DN, we investigated the effect of MOR on an in vitro model of lipid metabolism disorder of DN established by stimulating mouse renal tubular epithelial cells (mRTECs) with sodium palmitate (PA) or high glucose (HG). Oil Red O and filipin cholesterol staining assays were used to determine intracellular lipid accumulation status. Results revealed that PA or HG stimulation inhibited the expressions of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), liver X receptors (LXR), ATP-binding cassette subfamily A member 1 (ABCA1), ABCG1, and apolipoprotein E (ApoE) in mRTECs as evidenced by western blot and quantitative real-time PCR, resulting in increased intracellular lipid deposition. Interestingly, MOR upregulated expressions of PGC-1α, LXR, ABCA1, ABCG1, and ApoE, thus reducing cholesterol accumulation in mRTECs, suggesting that MOR might promote cholesterol efflux from mRTECs via the PGC-1α/LXR pathway. Of note, silencing PGC-1α reversed the promotive effect of MOR on PA- or HG-induced cellular cholesterol accumulation. In conclusion, our results suggest that MOR has a protective effect on mRTECs under high lipid or high glucose conditions, which may be related to the promotion of intracellular cholesterol efflux mediated by PGC-1α.
Subject(s)
Glucose/administration & dosage , Glycosides/pharmacology , Kidney Diseases/metabolism , Kidney Tubules/drug effects , Lipid Metabolism Disorders/drug therapy , Palmitic Acid/pharmacology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Animals , Cell Line , Enzyme Inhibitors/pharmacology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Kidney Tubules/metabolism , Kidney Tubules/pathology , Lipid Metabolism Disorders/etiology , Lipid Metabolism Disorders/metabolism , Lipid Metabolism Disorders/pathology , Mice , Plant Extracts/pharmacology , Signal Transduction , Sweetening Agents/pharmacologyABSTRACT
This paper was aimed to establish a new method for evaluating the anaphylactoid reaction of 15 batches of Zushima Injection from different manufacturers in vitro. Basophilic leukemia cell line RBL-2 H3 cells were cultured in vitro and Compound 48/80 was selected as positive drug. Real-time cell analysis(RTCA) system was used to detect the changes of cell index(CI) value after drug intervention. The degranulation of RBL-2 H3 cells was verified with the toluidine blue staining technology by observing the changes of cell morphology and skeleton. Clustering method was used to analyze the CI values of 15 batches of Zushima Injection on RBL-2 H3 cells. The results showed Compound 48/80(20 µg·mL~(-1)) significantly changed the cell morphology and cytoskeleton, with obvious degranulation. After adding Compound 48/80, CI value decreased rapidly within 30 minutes, then decreased slowly, suggesting that RTCA system can be used for rapid and sensitive evaluation of RBL-2 H3 cell degranulation. The results of cluster analysis showed that Zushima Injection from different manufacturers had different effects on RBL-2 H3 cells. S1-S8 and Compound 48/80 groups were grouped into one cluster, which suggesting that the sample might have potential clinical anaphylaxis. S9-S15 and the normal control group were grouped into one cluster, suggesting there was no anaphylactoid reaction in the sample. In this study, a rapid in vitro anaphylaxis evaluation technique based on RTCA system and pattern recognition method was established, which can be used for rapid in vitro evaluation of anaphylaxis for traditional Chinese medicine injection.
Subject(s)
Anaphylaxis , Cell Degranulation , Humans , Mast Cells , Medicine, Chinese Traditional , p-Methoxy-N-methylphenethylamineABSTRACT
Context: Chloranthus serratus [(Thunb.) Roem. et Schult, (Chloranthaceae)] is a folk medicine used for the treatment of rheumatoid arthritis.Objective: The aim of this study was to investigate anti-arthritic effects of the ethanol extracts of the roots (ER), stems (ES) and leaves (EL) of C. serratus on adjuvant arthritis rats and related mechanisms.Materials and methods: The rats were immunized by intradermal injection of complete Freund's adjuvant (CFA, 0.18 mL) into the right hind feet, and received intragastric administrations of the ER, ES and EL (2.07, 1.61 and 0.58 g/kg/d, respectively) for 14 days. The anti-arthritic activity was assessed by swelling rates, serum indicators, antioxidant capacity, histopathological and immunohistochemical analyses.Results: The LD50 of the ER, ES and EL was higher than 10.35, 8.05 and 2.90 g/kg/p.o., respectively. Extract treatments decreased swelling rates, tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 1 beta (IL-1ß), migration inhibitory factor 1 (MIF-1), immunoglobulin G (IgG) and immunoglobulin M (IgM) levels and positive expression of VEGF in the arthritic rats (p < 0.01 or p < 0.05). The ER significantly decreased NO (3.91 ± 0.61 µmol/L), IL-6 (75.67 ± 16.83 pg/mL) and malondialdehyde (MDA) (2.28 ± 0.32 nmol/mL) contents and clearly increased IFN-γ (2082 ± 220.93 pg/mL) and superoxide dismutase (SOD) (601.98 ± 38.40 U/mL) levels. The ES and EL did not reverse the changes in some indicators. All the extracts alleviated inflammatory cell infiltration and synovial cell proliferation. Among them, the ER was the most pronounced.Discussion and conclusions: ER exerts the most promising effects, as shown by inhibiting the releases of inflammatory cytokines and enhancing antioxidant capacity, which provides a scientific basis for further research on C. serratus and its clinical applications.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/drug therapy , Drugs, Chinese Herbal/therapeutic use , Plant Leaves , Plant Roots , Plant Stems , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antirheumatic Agents/isolation & purification , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Arthritis, Experimental/blood , Arthritis, Experimental/pathology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Freund's Adjuvant , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/blood , Male , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats , Rats, Sprague-Dawley , Treatment OutcomeABSTRACT
BACKGROUND AIMS: The use of bone marrow mononuclear cells (BM-MNCs) has achieved great outcomes in clinical practice. We aim to evaluate the efficacy and safety of autologous BM-MNC infusion and hyperbaric oxygen therapy (HOT) in type 2 diabetes mellitus. METHODS: This single-center, randomized, open-label, controlled clinical trial with a factorial design included two phases. The patients received standard medical therapy in the run-in phase; in the treatment phase, patients with glycated hemoglobin of 7.5-9.5% were randomly assigned into four groups and underwent BM-MNC infusion along with HOT (BM-MNC+HOT group), BM-MNC infusion (BM-MNC group), HOT (HOT group) and standard medical therapy (control group), respectively. The area under the curve of C-peptide was recorded as a primary end point. Our research is registered at ClinicalTrials.gov (NCT00767260). RESULTS: A total of 80 patients completed the follow-up. At 12 months after treatment, the area under the curve of C-peptide (ng/mL per 180 min) of the BM-MNC+HOT group and the BM-MNC group were significantly improved (34.0% and 43.8% from the baseline, respectively). The changes were both significant compared with that in the control group, but no remarkable change was observed in the HOT group. Treatment-related adverse events were mild, including transient abdominal pain (n = 5) and punctual hemorrhage (n = 3). CONCLUSIONS: BM-MNC infusion for type 2 diabetes mellitus improves islet function and metabolic control, with mild adverse effects. HOT does not synergize with BM-MNC infusion.
Subject(s)
Bone Marrow Cells/metabolism , Cell Transplantation , Diabetes Mellitus, Type 2/therapy , Hyperbaric Oxygenation , Insulin-Secreting Cells/metabolism , Leukocytes, Mononuclear/transplantation , Aged , Bone Marrow Cells/pathology , Cells, Cultured , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Insulin-Secreting Cells/pathology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Treatment OutcomeABSTRACT
This paper mainly examined the anti-osteosarcoma activity of total flavonoids extract from traditional Chinese medicine, nidus vespae. Orthogonal design was used to design the extraction process of total flavonoids. L(3(4)) orthogonal test was performed and the extracts obtained by three optimal extraction processes were used for anti-tumour activity screening in order to determine the optimal anti-tumour effective component of nidus vespae. MTT assay was used to investigate the effect of nidus vespae extract on proliferation activity of osteosarcoma cells. Meanwhile, U2OS cell inhibitory capacities of extracts in three groups with higher total flavonoid contents were investigated and compared, and inhibition rates were calculated. The results showed that the optimal extraction process was ethanol concentration of 95%, 12-fold amount of ethanol relative to the weight of medicinal material, extraction times of 3 times, and extraction time of 2 hours. 9 extraction processes all showed proportional trend of cancer cell inhibition rate to extract concentration.