Chinese Medicine Enhancing Response Rates to Immunosuppressant PD-L1 Inhibitor and Improving the Quality of Life of Hepatocellular Carcinoma-Bearing Mice.

Background: Malignant tumors are a significant disease endangering human health. Chinese Medicine (CM) plays an important role in comprehensive and holistic tumor treatment. Objectives: We aimed to investigate whether CM combined with the immunosuppressant PD-1/PD-L1 inhibitor has a good synergistic effect and can significantly improve response rates for the immunosuppressant. Methods: We combined CM with immunosuppressant in treating six-week-old hepatocellular carcinoma-bearing mice and compared the outcomes of groups undergoing different interventions: blank group, control group, CM group, PD-L1 inhibitor group, and CM + PD-L1 inhibitor group, with ten mice in each group. The quality of life was evaluated along with the tumor inhibition effects and growth rates. Results: CM significantly reduced tumor load and improved the quality of life of cancer-bearing mice. The survival rate was 81.8% in the control group, 100% in the CM group, 90.9% in the PD-L1 inhibitor group, and 100% in the combined group in the first week. The survival rate was 45.5% in the control group, 54.5% in the CM group, 81.8% in the PD-L1 inhibitor group, and 81.8% in the combined group in the second week. 38% mice in the CM+PD-L1 inhibitor group with smaller tumor size than the average of the control group, which was much higher than other treatment groups. CM also reduced the expression of JAK2 mRNA and STAT3 mRNA, although not significantly (P > 0.05), and reduced PD-L1 mRNA in tumor tissue compared to the control group (P < 0.05). Conclusions: CM had a synergistic effect on PD-L1 inhibitors and increased response rates to PD-L1 inhibitor treatment.

The Role of Complementary and Alternative Medicine on Cancer-Related Fatigue in Adults: An Overview of Systematic Reviews.

BACKGROUND: Cancer-related fatigue (CRF) has an enormous adverse impact on quality of life and subsequent therapy of cancer patients. Complementary and alternative medicine (CAM) is reported to improve CRF in many systematic reviews (SRs), but the effects are controversial because of variations in the quality and outcomes. METHODS: Thirteen databases were searched from inception to September 2022. Only SRs of randomized controlled trials (RCTs) were included. We assessed the quality of included SRs with the AMSTAR-2 tool, the strength of evidence with the GRADE system, the risk of bias with the ROBIS tool, and the integrity of SRs with the PRISMA checklist. RESULTS: We included 30 eligible SRs (27 meta-analyses). Based on the AMSTAR-2 tool, 29 SRs were rated as "critically low" quality, and only one was rated as "low" quality. With the ROBIS tool, 19 SRs demonstrated a low risk of bias. According to the PRISMA checklist, no SRs reported all the items, and 10 SRs sufficiently reported over 70%. Based on the GRADE system, 7 outcomes were assessed as high-quality evidence. CONCLUSION: This overview demonstrates promising evidence for the effectiveness of CAM interventions in the treatment of CRF in adults. The roles of qigong, music, auricular point therapy, and dietary supplements in CRF need further evaluation. Although findings are mixed, it is recommend to select appropriate CAM to manage cancer-related fatigue under the guidance of physicians. More studies with rigorous methodological designs and sufficient sample sizes are needed.

Efficacy and safety of oral Chinese medicine on cancer-related fatigue for lung cancer patients after chemotherapy: Protocol for systematic review and meta-analysis.

INTRODUCTION: Lung cancer has the highest mortality rate of about 18.0% among malignant tumors worldwide, and chemotherapy is the main treatment. 80% of patients receiving chemotherapy suffers from cancer-related fatigue, which is the most severe symptom, with a large effect on quality of life as well as prognosis. Oral Chinese medicine, a kind of complementary and alternative medicine, has been proved to benefit lung cancer patients. However, no studies have reviewed whether it can reduce fatigue in lung cancer patients after chemotherapy, which is the purpose of our study. METHODS: Two reviewers will systematically and independently retrieve papers, select studies for inclusion, extract data, and assess risk of bias. The following nine databases will be searched: China National Knowledge Infrastructure, Wan Fang database, Chinese Scientific Journals Database, Chinese biomedical literature service system, PubMed, Web of Science, OVID, Scopus, and EMBASE from inception to February, 2022. Included studies will only be randomized controlled trials. Primary outcome is cancer-related fatigue. Secondary outcomes are quality of life, immunologic function, and the incidence of adverse events. We will use RoB 2 tool to assess the risk of bias and RevMan to analyze data. Risk ratios will be calculated for dichotomous data and mean differences for continuous data. Random-effect model will be used to integrate statistical effects. Meta-regression, subgroup and sensitivity analyses will be carried out. We will evaluate the strength and overall quality of evidence with four levels: very low, low, moderate, and high. RESULTS: The review of current evidence of oral Chinese medicine on cancer-related fatigue for lung cancer patients after chemotherapy will be narratively summarized and quantitatively analyzed. CONCLUSION: The definitive conclusion will help physicians to determine whether oral Chinese medicine is an effective treatment for reducing fatigue in lung cancer patients after chemotherapy in clinical settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021292576.

Pharmacokinetics and pharmacodynamics of rhubarb anthraquinones extract in normal and disease rats.

BACKGROUND: Anthraquinones extract from Rheum palmatum L. (rhubarb) including rhein, emodin, aloe-emodin, chrysophanol, physcion and sennoside A, has been widely used in China to treat various diseases. OBJECTIVE: This study was designed to explore the pharmacokinetic and pharmacodynamic properties of rhubarb anthraquinones extract in diabetic nephropathy and acute liver injury rats. METHODS: The diabetic nephropathy and acute liver injury rats were induced by intraperitoneal injection with streptozotocin (STZ) and carbon tetrachloride (CCL4), respectively. The rats were treated with different doses of rhubarb anthraquinones extract (37.5, 75 and 150mg/kg) as administration groups. For pharmacokinetics, the drug concentrations of rhubarb anthraquinones consisting of rhein, emodin, aloe-emodin, chrysophanol, physcion and sennoside A were determined. For pharmacodynamics, the anti-diabetic nephropathy and hepatoprotective effects were assessed under different dosage regimens. RESULTS: The rhein, emodin, aloe-emodin, chrysophanol were considered as pharmacokinetic markers at three doses of rhubarb anthraquinones extract. In diabetic nephropathy rats, no obvious pharmacokinetic change of the four ingredients was observed compared with control rats. However, the plasma exposures of the four ingredients increased in acute liver injury rats compared with control rats. The serum creatinine (SCr), blood urea nitrogen (BUN) and urine protein (UP) values in diabetic nephropathy rats decreased compared with those in the model group, which suggested that rhubarb anthraquinones extract displayed certain therapeutic and preventive effects against the diabetic nephropathy. However, rhubarb anthraquinones extract cannot ameliorate the CCL4-induced liver injury under the three different dosage regimens. CONCLUSION: There was no significant pharmacokinetic difference after a single oral administration of rhubarb anthraquinones extract between control and diabetic nephropathy rats. However, apparent pharmacokinetic differences were observed between control and liver injury rats. Also, rhubarb anthraquinones extract had beneficial effects on diabetic nephropathy rats, while no marked effect on liver injury rats under the same dosage regimens.

Magnesium Isoglycyrrhizinate attenuates lipopolysaccharide-induced depressive-like behavior in mice.

Magnesium Isoglycyrrhizinate (MI) is a magnesium salt of 18α-GA stereoisomer which has been reported to exert hepatoprotective activity. The aim of the present study was to ascertain the underlying mechanisms behind the action of Magnesium Isoglycyrrhizinate on neuroinflammatation and oxidative stress in LPS-stimulated mice. Mice were pretreated with Magnesium Isoglycyrrhizinate (MI, 25, 50mg/kg) as well as fluoxetine (Flu, positive control, 20mg/kg) once daily for one week before intraperitoneal injection of LPS (0.83mg/kg). Pretreatments with MI and Flu significantly improved immobility time in tail suspension test (TST) and forced swim test (FST) as well as locomotor activity in open-field test (OFT). In addition, the levels of pro-inflammatory cytokines and oxidative stress in serum and hippocampus were also suppressed effectively by MI and Flu administrations. Western blot analysis showed the up-regulated levels of p-Jak3, p-STAT3, p-NF-κBp65, and p-IκBα in mice exposed to LPS, while different degrees of down-regulation in these expression were observed in MI (25, 50mg/kg) and Flu (20mg/kg) groups respectively. Taken together, our obtained results demonstrated that Magnesium Isoglycyrrhizinate (MI) exhibited an antidepressant-like effect in LPS-induced mice, which might be mediated by JAK/STAT/NF-κB signaling pathway.

The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state.

Inflammation response and oxidative stress have been reported to be involved in the pathogenesis of acute lung injury (ALI). Accordingly, anti-inflammatory treatment is proposed to be a possible efficient therapeutic strategy for ALI. The purpose of our present study was to evaluate the anti-inflammatory efficacy of trillin (Tr) on ALI induced by lipopolysaccharide (LPS) in mice and explore the underlying mechanism. BALB/c mice received Tr (50, 100 mg/kg) intraperitoneally 1 h prior to the intratracheal instillation of lipopolysaccharide (LPS) challenge. Pretreatment with Tr at the dose of 50, 100 mg/kg markedly ameliorated lung wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and pulmonary histopathological conditions. In addition, the protective efficacy of Tr might be attributed to the down-regulations of neutrophil infiltration, malondialdehyde (MDA), inflammatory cytokines and the up-regulations of super-oxide dismutase (SOD), catalase(CAT), glutathione(GSH), Glutathione Peroxidase(GSH-Px) in bronchoalveolar lavage fluid (BALF). Meanwhile, our study revealed some correlations between (NF-E2-related factor 2) Nrf2/heme oxygenase (HO)-1/nuclear factor-kappa B (NF-κB) pathways and the beneficial effect of Tr, as evidenced by the significant up-regulations of HO-1 and Nrf2 protein expressions as well as the down-regulations of p-NF-κB and p-inhibitor of NF-κB (IκB) in lung tissues. Taken together, our results indicated that Tr exhibited protective effect on LPS-induced ALI by the regulations of related inflammatory events via the activations of Nrf2, HO-1 and NF-κB pathway. The current study indicated that Tr could be a potentially effective candidate medicine for the treatment of ALI.