Effects of Oral Administration of D-002 (Beeswax Alcohols) on Histological and Functional Outcomes in a Rat Model of Antigen-Induced Arthritis: Preliminary Study

Abstract

Abstract. D-002, a mixture of higher aliphatic beeswax alcohols, has been shown to display antiinflammatory effects associated with the dual inhibition of ciclooxygenase and 5-lipoxygenase. Oral D-002 supplementation has been effective in experimental osteoarthritis, ameliorating all features of joint histopathology. Clinical studies have demonstrated that D-002 reduces osteoarthritis symptoms. However, D-002 effects on experimental models of rheumatoid arthritis (RA) have not been evaluated. To investigate whether D-002 improves histopathological and functional outcomes in a rat model of antigen-induced arthritis. First experiment. Rats were randomized into a negative vehicle-control (sham) and four groups injected with complete Freund's adjuvant (CFA): a positive vehicle-control, three treated with D-002 (50, 200 and 400 mg/kg/day) for 21 days. Second experiment. Rats were randomized into a sham and four CFA-injected groups: a positive vehiclecontrol, two treated with D-002 (25 and 100 mg/kg/day), one with methorexate (MTX) (0.3 mg/kg) for 28 days. Arthritis severity was evaluated by bodyweight loss, decreased exploratory activity and histological changes of tarsal joint and spleen samples in both experiments, except the exploratory activity, assessed only in the first one. CFA injection decreased the bodyweight and the exploratory activity, and induced infiltration of mononuclear cells, pannus formation and vascularity in the tarsal joint of positive control rats. These changes were significantly and markedly ameliorated by D-002 as compared to the positive control. MTX also reversed CFA-induced changes. The reduction of the infiltration of mononuclear cell with D-002 400 mg/kg was greater (80.9%) than with MTX (66.8%), but effects on other variables were similar. No abnormalities in spleen samples of D-002-treated groups were detected. This is the first report demonstrating the efficacy of oral treatment with D-002 in a rat model of antigen-induced arthritis. Results suggest that D-002 could help manage RA, but confirmation of such potential benefit requires extensive further research.

Enhancement of Antioxidant and Anti-Glycation Properties of Beeswax Alcohol in Reconstituted High-Density Lipoprotein: Safeguarding against Carboxymethyllysine Toxicity in Zebrafish

“…Despite the many papers from animal and human studies showing that supplementation of BWA ameliorated gastric ulcers, esophagitis, and osteoarthritis [10,11,56], the in vitro antioxidant abilities of BWA and the mechanism of antioxidant activity after oral ingestion were not fully elucidated. Although BWA has adequate DPPH radical scavenging activity and ferric ion reduction ability in ethanol solvent assay systems [57], the current results showed that the incorporation of BWA in rHDL resulted in more enhancement of HDL-associated PON and FRA activity to inhibit LDL oxidation.…”

“…Beeswax alcohol (BWA), a beeswax-extracted substance, comprises a blend of six main aliphatic alcohols (of carbon chains 24, 26, 28, 30, 32, and 34) that demonstrate antioxidant, anti-platelet, cholesterol-lowering, and gastroprotective properties [8,9]. Notably, supplementing with BWA enhanced the production and quantity of gastric mucus in rat models with ethanol-induced ulcers and mitigated inflammation in cases of antigen-induced arthritis [10,11]. BWA is acknowledged for safeguarding the body against oxidative stress, promoting a healthy stomach by protecting the gastric mucosa, and contributing to maintaining joint health.…”

Enhanced Antioxidant and Anti-Glycation Abilities of Beeswax Alcohol in Reconstituted High-Density Lipoprotein with Potent Wound-Healing Activity and Protection of Embryo from Acute Toxicity of Carboxymethyllysine in Zebrafish

“…Despite the many papers from animal and human studies showing that supplementation of BWA ameliorated gastric ulcers, esophagitis, and osteoarthritis [10,11,50], the in vitro antioxidant abilities of BWA and the mechanism of antioxidant activity after oral ingestion were not fully elucidated. Although BWA has adequate DPPH radical scavenging activity and ferric ion reduction ability in ethanol solvent assay systems [52], the current results showed that the incorporation of BWA in rHDL resulted in more enhancement of HDL-associated PON and FRA activity to inhibit LDL oxidation.…”

“…Beeswax alcohol (BWA), a substance purified from beeswax, contains a mixture of six primary aliphatic alcohols (C24, C26, C28, C30, C32, and C34) with antioxidant, anti-platelet, cholesterollowering, and gastroprotective effects [8,9]. In particular, BWA supplementation promoted the secretion and quality of gastric mucus in ethanol-ulcer rat models and attenuated inflammation in antigen-induced arthritis [10,11]. With these properties, BWA has been registered as a functional food ingredient to help protect the body from oxidative stress, maintain a healthy stomach by protecting the gastric mucosa, and maintain joint health in Korean health functional foods according to the Ministry of Food and Drug Safety (MFDS, https://www.foodsafetykorea.go.kr/portal/board/board Detail.do?menu_grp=MENU_NEW01&menu_no=2660&bbs_no=bbs987&nticmatr_yn=N&bbs_type _cd=01&ans_yn=N&ntctxt_no=21590).…”

Beeswax Alcohol (BWA) Protects Lipoproteins From Oxidation to Rescue Embryo Death From Acute Toxicity and to Exert Antioxidant Activities in Serum of Subjects With Sixties Individuals After 12 Weeks Consumption of BWA 100 mg/Day

“…However, the most noteworthy role of BWA was established as a gastroprotective agent. Several pharmacological and clinical studies confirmed the impact of BWA on the quantity and quality of gastric mucous [14,15]. Recently, the Korean Food and Drug Administration (KFDA) approved BWA as a functional food ingredient for improving joint and gastrointestinal health [12].…”