Rhubarb and Oxalosis (Rheum Species)

Plant-based foods have been established as “natural medicines” for their potential pharmacological properties. Chinese rhubarb plants – belonging to Polygonaceae family, are traditionally used to ameliorate digestive system problems. This study evaluated the chemical profile and bioactivities of three Rheum species – R. officinale (RO), R. palmatum (RP), and R. tanguticum (RT) roots.

Five crude root extracts – water (W), ethanol (EtOH), acetone (A), ethyl acetate (EA), and hexane (H) – were tested for phytochemical screening, antioxidant tests, HPLC analysis, and dual-chambered-MFCs for bioenergy production. Molecular docking analysis of chemical markers was implemented to establish its application for antiviral drug development.

Both RO and RP possessed the highest polyphenols and flavonoids in EA and H extracts, respectively. RT-A contained the highest phytochemical constituents compared to other solvent extracts. The RT-A extract demonstrated the highest scavenging activity against DPPH (IC₅₀=0.042±0.000mg/mL) and contained the highest FRAP value (1051.238±7.154mg Trolox/g). Bioenergy evaluation showed that RO-W exhibited the highest bioenergy-stimulating capabilities (1.84 fold power amplification). Furthermore, rhein from the same extract possessed the efficient electron-shuttling ability. Molecular docking analysis showed that Rheum metabolites inhibited key enzymes (i.e. RdRp and ACE-2) of SARS-CoV-2 viral replication process. Rhein (∆G=-6.9 kcal/mol) and chrysophanol (∆G=-4.8 kcal/mol) owned the highest binding affinity with RdRp and ACE-2 of SARS-CoV-2, respectively. This study provided a novel basis for the potential utilization of Rheum species as a renewable material for bioprocess engineering and electro-fermentation. Moreover, molecular docking analyses on Rheum species metabolites against SARS-CoV-2 offered a new rationale as a medicinal herb for antiviral drug development.

Rhubarb, in the form of a traditional Chinese medicine, is used in the treatment of chronic kidney disease (CKD). Previous studies have demonstrated that Rhubarb possesses a good nephroprotective effect, which primarily protects the kidneys from fibrosis, oxidation, inflammation, autophagy, and apoptosis. However, studies have shown that the long-term inappropriate use of Rhubarb may cause damage to renal function. Therefore, how to correctly understand and scientifically evaluate the pharmacodynamics and toxicity of Rhubarb with regard to CKD is a scientific question that urgently needs to be answered. In this review, we explain and illustrate how Rhubarb exerts its nephroprotective effect against CKD. We also describe the mechanisms of action that may cause its nephrotoxicity. Valuable and practical clinical guidance is proposed with regard to methods for mitigating the nephrotoxicity of Rhubarb.

The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored.

To evaluate the safety of NDQG in kidney disease treatment.

The literature was searched in Embase, Medline via PubMed, Cochrane Library database, Wanfang database, Chinese National Knowledge Infrastructure, SinoMed, and Chinese VIP Database from inception to January 15, 2022, for randomized controlled trials (RCTs) and observational studies. The ClinicalTrials.gov website was searched for ongoing trials. The frequency and characteristics of adverse drug reactions (ADRs) were the primary and secondary outcomes, respectively. Subgroup analysis were conducted to explore the effects of clinical trial types, different kidney diseases, drug combinations and dosage on the safety of NDQG.

This review included 132 trials comprising 115 RCTs and 17 cohort studies. Additionally, 118 studies reported ADR rates with complete data, including 10381 participants. Regarding ADR frequency, no significant difference was observed between NDQG (7.26%) and control (8.39%) groups (RR = 0.890, 95% confidence interval (CI): 0.788–1.007); with no heterogeneity among the studies (I² = 0.0%, P = 0.958). ADR frequency in patients with chronic kidney disease (65 trials, n = 5823) was significantly lower in the NDQG treatment group than in the control group (RR = 0.810, 95% CI: 0.67–0.969, I² = 0.0%, P = 0.993); however, for patients with diabetic nephropathy there was no difference between both groups (26 trials, n = 2166, RR = 1.077, 95% CI: 0.802–1.446, I² = 0.0%, P = 0.611). Similarly, the incidence of ADR in patients on dialysis and patients with pyelonephritis and nephrotic syndrome was the same for both groups, with 95% CI overlapping the line. For different interventions, including NDQG monotherapy or its combination with other commonly used drugs (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin drugs, and compound α-keto acid) or dialysis, the incidence of ADR showed no significant difference between the experimental and control arms. The ADR in the NDQG group primarily affected the gastrointestinal system (64.74%), central and peripheral nervous system (9.07%), whole body (5.79%), and skin and appendages (4.53%). The most common clinical manifestations were diarrhea, nausea, and vomiting.

Our meta-analysis showed that compared with supportive therapy, the incidence of ADR was similar when NDQG was added. However, current evidence is not definitive and more well-designed and conducted RCTs are warranted to definitively establish the reliable evidence.

PROSPERO CRD 42018104227

Chronic alcohol consumption, which is observed worldwide, can damage pancreatic tissue and promote pancreatitis. Rhubarb is a widely used traditional Chinese herbal medicine for treating pancreatitis in China. However, few pharmacological studies have investigated its epigenetic regulation. In this study, we investigated whether chronic exposure to alcohol can alter inflammatory gene expression and the epigenetic regulation effect of cooked rhubarb in the pancreatic tissue of rats. First, changes in inflammatory cytokine DNA methylation (IL-10, IL-1α, TNF-α, NF-κB and TGF-β) were detected in pancreatic tissue of Sprague-Dawley rats with varying alcohol exposure times (4, 6, 8, or 12 weeks), and then with varying doses of cooked rhubarb treatment (3, 6, or 12 g/day). DNA methylation levels, related RNA concentrations and protein expression of specific inflammatory cytokines, and histopathological score were analysed in pancreatic tissue of Sprague-Dawley rats. The results showed that chronic alcohol exposure (8 weeks) reduced the level of IL-1α DNA methylation and increased its protein expression in acinar cells (P < 0.05). In the acinar cells, the level of IL-10 DNA methylation increased, resulting in a reduction of protein expression (P < 0.05). Simultaneously, chronic alcohol exposure increased the pathological damage to the pancreas (P < 0.05). Finally, cooked rhubarb treatment (3 g/kg/day) effectively alleviated these changes in pancreatic tissue from chronic alcohol exposure (P < 0.05). These results indicate that chronic exposure to alcohol leads to changes in DNA methylation and protein expression of inflammatory genes, and cooked rhubarb may have a protective effect on the pancreatic tissue of rats.

Rhubarb petioles are usually cooked for a tasty and well-liked dessert, but they contain high levels of oxalates known to be potent toxins. This work aimed to study on oxalate bioaccessibility of a food containing high oxalates using an in vitro digestion system. Cooking rhubarb petioles with water, trim or standard milk significantly (p < 0.05) reduced oxalate contents of the mixture by dilution (total oxalate mean raw 902.7 mg/100 g fresh weight, mean cooked 454.3 mg/100 g fresh weight). Total reduction of soluble oxalate amounts cooked with trim and standard milk were 65.9 % and 74.5 %, respectively when compared to those in the raw petioles. In the intestinal segment, significantly lower amounts of soluble oxalates (lower 8 % - 36 %) are available for absorption compared to those measured by the chemical extraction. A standard serving of boiled rhubarb contains high levels of soluble oxalate which is significantly reduced by 70.3 % when it is cooked with milk. Overall, the data suggests that less soluble oxalates available for absorption in the in vitro digestion than those reported by chemical extractions. Cooking a food containing high oxalates, especially rhubarb stalks, with milk would be an effective way to reduce soluble oxalate intakes for people suffering from kidney stone.