Eight previously undescribed lanostane triterpenoids, including five nortriterpenoids with 26 carbons, ganothenoids A-E (1-5), and three lanostanoids, ganothenoids F-H (6-8), along with 24 known ones (9-32), were isolated from the fruiting bodies of Ganodrma theaecolum. The structures of the novel compounds were elucidated using comprehensive spectroscopic methods, including electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations. Compounds 1-32 were assessed for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Compound 4 demonstrated the most potent neuroprotective activity against H₂O₂-induced oxidative stress by suppressing G₀/G₁ phase cell cycle arrest, reducing reactive oxygen species (ROS) levels, and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein (Bcl-2) and Bcl-2 associated X-protein (Bax) protein expression. Compounds 26, 12, and 28 exhibited PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μmol·L^-1, while compound 12 alone displayed significant inhibitory effects on α-glucosidase with an IC₅₀ value of 43.56 μmol·L^-1. Additionally, enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B and α-glucosidase, respectively.
Humans ; Fruiting Bodies, Fungal/chemistry* ; Triterpenes/isolation & purification* ; Neuroprotective Agents/isolation & purification* ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism* ; Ganoderma/chemistry* ; Apoptosis/drug effects* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; alpha-Glucosidases/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Oxidative Stress/drug effects* ; Hydrogen Peroxide/toxicity* ; Molecular Docking Simulation

Objective:To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke patients with multiple organ dysfunction syndrome (MODS).Methods:A retrospective and observational study was conducted. A total of 15 patients with heat stroke combined with MODS who were admitted to the department of intensive care unit (ICU)of Suizhou Central Hospital/Hubei University of Medicine from July to September 2022 were selected as the study objects. All 15 patients were treated with CVVHDF combined with HA380 based on the comprehensive management strategy for severe illness. Organ function indicators [including total bilirubin (TBil), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr), cardiac troponin T (cTnT), myoglobin (Myo), MB isoenzyme of creatine kinase (CK-MB), sequential organ failure assessment (SOFA)] and inflammatory indicators [including white blood cell count (WBC), neutrophil count (NEU), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)] were collected. The improvements of the above indexes at admission, after the first HP, after the second HP, after the third HP, and on the 5th day of treatment were compared. Combined with the clinical outcome of patients, the comprehensive efficacy of CVVHDF combined with HA380 in the treatment of severe heat radiation disease was evaluated.Results:There were 10 males and 5 females among the 15 patients. The average age was (64.5±11.5) years old. There were 6 cases of classical heat stroke and 9 cases of exertional heat stroke. Glasgow coma scale (GCS) was 3-8 at admission; SOFA score was 9-17 within 12 hours after admission; acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) was 25-45 within 24 hours after admission. After treatment, the IL-6 level and SOFA score gradually decreased, and there were significant differences in the decrease after the second HP compared to admission [IL-6 (ng/L): 48.37 (15.36, 113.03) vs. 221.90 (85.87, 425.90), SOFA: 8.3±3.3 vs. 11.1±2.4, both P < 0.05]. The PCT level reached its peak after the first HP [12.51 (6.07, 41.65) μg/L], and then gradually decreased, and the difference was statistically significant after the third HP [1.26 (0.82, 5.40) μg/L, P < 0.05]. Compared those at admission, Cr level significantly improved after the first HP (μmol/L: 66.94±25.57 vs. 110.80±31.13, P < 0.01), Myo significantly decreased after the second HP [μg/L: 490.90 (164.98, 768.05) vs. 3?000.00 (293.00, 3?000.00), P < 0.05], After the third HP, the CK level also showed significant improvement [U/L: 476.0 (413.0, 922.0) vs. 2?107.0 (729.0, 2?449.0), P < 0.05]. After CVVHDF combined with 3 times HP treatment, the patient's inflammatory response was gradually controlled and organ function gradually recovered. On the 5th day of the disease course, WBC, PCT and IL-6 levels were significantly improved compared to admission, and AST, CK, LDH, Cr, Myo, CK-MB, and SOFA score were significantly corrected compared with those on admission. The 24-hour survival rate of 15 patients was 86.67%, and the 24-hour, 7-day and 28-day survival rates were both as high as 73.33%. The average mechanical ventilation time of 11 surviving patients was (101.8±22.0) hours, the average continuous renal replacement therapy (CRRT) time was (58.8±11.0) hours, the average length of ICU stay was (6.3±1.0) days, and the average total hospitalization was (14.6±5.2) days. Conclusion:CVVHDF combined with HP HA380 in the treatment of heat stroke patients with MODS can effectively improve organ function and alleviate the inflammatory storm, which is an effective means to improve the rescue rate and reduce the mortality of severe heat stroke patients.

Objective To observe the effects ofLiuwei Dihuang Decoction on cAMP and PDE3B in adipose tissues of rats with type 2 diabetes;To explore its mechanism.MethodsTotally 80 SD rats were randomly divided into two groups:control group and molding group. Rats in the molding group established the type 2 diabetic models by feeding high sugar and fat diet combined with intraperitoneal injection of Streptozotocin. The successful modeling rats were divided into model group, Rosiglitazone group, andLiuwei Dihuang Decoction group. Administration groups were given relevant medicine for gavage, while model group and blank group were given the same amount of normal saline for 30 days. FBG levels were detected, and cAMP and INS levels were detected by ELISA. The protein expressions of PDE3B in adipose tissues were determined by Western blot. The mRNA expressions of PDE3B in adipose tissues were detected by RT-PCR.Results Compared with the model group, the FBG and INS levels in type 2 diabetic rats were reduced in Rosiglitazone group andLiuwei DihuangDecoction group (P<0.05,P<0.01). InLiuwei Dihuang Decoction group, the protein and mRNA expressions of PDE3B in the adipose tissues were higher, and cAMP levels were lower than the model group (P<0.01).ConclusionLiuwei Dihuang Decoction can increase PDE3B expression, and decrease cAMP level, which may be one of the mechanisms for improving insulin resistance in type 2 diabetic rats.