Neutrophil elastase inhibitory effects of pentacyclic triterpenoids from Eriobotrya japonica (loquat leaves)

Abstract

Ethnopharmacological relevance: Eriobotrya japonica, a traditional herbal medicine in China and Japan, has long been used to treat chronic bronchitis and coughs. Aim of the study: Pentacyclic triterpenoids (PTs), especially ursolic acid (UA), have been found as reversibly and competitively human neutrophil elastase (HNE) inhibitors. However, the limited solubility and poor bioavailability of PTs hinder their clinical use. Crude plant extracts may have a greater activity than isolated constituents of the equivalent dosage. In this study, an Eriobotrya japonica (loquat leaves) extract (triterpenoid composition of loquat leaves, TCLL) with enriched PTs such as UA was prepared. The study aims to compare the HNE inhibitory (HNEI) effect in vitro and the therapeutic effect on acute lung injury (ALI) in vivo between TCLL and UA. Materials and methods: An HNEI activity bioassay was performed with Sivelestat sodium hydrate as a positive control. A lipopolysaccharide (LPS)-induced lung inflammatory model was established to evaluate TCLL's therapeutic effect on ALI in vivo. The absorption of UA in TCLL and in UA alone was determined using a Caco-2 cell uptake model and LC-MS. Results: The IC 50 values of TCLL and UA for the HNEI effect were 3.26 ± 0.56 μg/mL and 8.49 ± 0.42 μg/mL (P < 0.01), respectively. TCLL significantly improved the inflammatory cells and inflammatory cytokine production in mice compared with the LPS group (P < 0.05). Additionally, it performed better than the UA alone group (P < 0.05). Moreover, the uptake by Caco-2 cells of UA in TCLL was higher than that in UA alone (P < 0.05). Conclusion: TCLL has a significant HNEI effect in vitro and a therapeutic effect on LPS-induced inflammation in a mouse model. Both the effects are more efficient than UA. Improved absorption of PTs in TCLL may be one explanation for these results.

Four sesquiterpene glycosides from loquat (Eriobotrya japonica) leaf ameliorates palmitic acid-induced insulin resistance and lipid accumulation in HepG2 Cells via AMPK signaling pathway

“…As an important traditional Chinese medicine, loquat leaf has been widely used with beneficial effects in numerous diseases including chronic bronchitis, asthma and diabetes (Fu et al, 2019;Kim, Paudel & Kim, 2020;Li et al, 2004;Zhang et al, 2019). Our previous study has confirmed the alleviation of hepatic lipid accumulation and hyperlipidemia of total SGs from loquat leaves in high-fat diet induced NAFLD mouse model.…”

“…The fruit tree, loquat (Eriobotrya japonica), is a small evergreen arbor and its leaf is an important traditional herbal medicine capable of counteracting inflammation, diabetes, and cancer (Liu et al, 2016). It has been reported that the chemical constituents of loquat leaf included phenolics (Fu et al, 2020), flavonoids (Lü et al 2009), terpenoids (Zhang et al, 2019), essential oils (Hong et al, 2010), sesquiterpene glycosides (SGs) (Ao et al, 2015) and polysaccharides (Lu et al, 2019). So far, the pharmacological activities of SGs in loquat were mainly manifested as hypoglycemic and anti-nonalcoholic fatty liver disease (NAFLD).…”

Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD-Induced Insulin Resistance by Modulating IRS-1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways

“…Besides, it has therapeutic potential for T2DM and obesity. The bioactivities of loquat leaf extracts or compounds have been authenticated scientifically and methodically by researchers, including anti-inflammation and antioxidation [ 16 , 40 – 42 ]. According to earlier studies, extracts of loquat leaves reduced TC and promoted glucose uptake in HFD-induced IR condition, which was instrumental in treating IR [ 43 , 44 ].…”

“…Besides, it has Oxidative Medicine and Cellular Longevity therapeutic potential for T2DM and obesity. The bioactivities of loquat leaf extracts or compounds have been authenticated scientifically and methodically by researchers, including anti-inflammation and antioxidation [16,[40][41][42].…”

Evolution from small molecule to nano-drug delivery systems: An emerging approach for cancer therapy of ursolic acid

“…Pentacyclic triterpenoids is an important class of bioactive natural compounds and which has gained much attention because of its superior therapeutic actions and fewer adverse effects in cancer therapy [12] , [13] , [14] . Ursolic acid (UA) (3b-hydroxy-urs-12-en-28-oic acid, Fig.…”