Limonin

Huazhuo Sanjie Chubi Decoction (HSCD), a Chinese herbal formula, is traditionally used for the treatment of spleen deficiency with dampness accumulation and is commonly used to treat gouty arthritis (GA). However, the potential active compounds and mechanisms of HSCD remain unclear.

To elucidate the key bioactive compounds and pharmacological mechanisms of HSCD in treating GA.

The chemical compounds in HSCD were qualitatively and quantitatively analyzed using ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Network pharmacology and molecular docking were employed to identify key active compounds and associated molecular pathways. Monosodium urate (MSU)-induced RAW264.7 macrophages and GA rat model were used to explore the potential therapeutic effects and mechanisms of HSCD in treating GA.

UPLC-MS/MS identified 184 compounds in HSCD, with 28 key compounds quantified. Network pharmacology revealed that verbenalin, limonin, and quercitrin are strongly associated with the molecular mechanisms of HSCD in treating GA via the PI3K-AKT signaling pathway. These compounds exhibited strong binding affinity to PI3K and AKT proteins. In RAW264.7 cells, HSCD and the three identified compounds dose-dependently reduced inflammation by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). They also downregulated both the PI3K-AKT and apoptosis signaling pathways. In rats, HSCD exerted therapeutic effects against acute GA by alleviating swelling and pathological damage to the ankle joints. Moreover, the molecular mechanisms in vivo were confirmed to be associated with the PI3K-AKT and apoptosis signaling pathways.

This study employed a multivariant approach to demonstrate the main bioactive compounds and molecular mechanisms of HSCD in treating GA, thereby supporting its traditional use.

The large number of by-products during the processing of citrus fruits exert significant pressure on the environment. Citrus by-products contain a variety of bioactive compounds that promote gut health and maintain microbial homeostasis. Therefore, recycling and reuse of these by-products is considered an excellent way to reduce environmental pressure. The purification and characterization methods of bioactive compounds (such as pectin, dietary fiber, polyphenols, essential oils, and limonin) extracted from citrus by-products in recent years are summarised. Subsequently, we summarize the digestive behavior (digestion, absorption, metabolism, and excretion) of these components, focusing on the mechanisms of action through which they exert prebiotic activity. This highlights the interactions between citrus by-product bioactives and gut microbiota, as well as the health effects on the host gut. Additionally, we provide a brief overview of the delivery systems for the active ingredients based on pectin from citrus sources. The results show that extraction methods can significantly affect the composition and structure of citrus by-products, which in turn affects digestive properties and eventually leads to differences in prebiotic activity. Notably, gut microbiota plays a key role in the metabolism and bioactivity of citrus actives. Besides, the innovative embedding methods can markedly enhance their prebiotic potential. Therefore, a comprehensive understanding of the relationship between the extraction, structure, and prebiotic activity of citrus by-products, as well as their delivery methods, is essential to advancing the use of citrus by-products in human health.