Combined Extracts of Epimedii Folium and Ligustri Lucidi Fructus with Budesonide Attenuate Airway Remodeling in the Asthmatic Rats by Regulating Apoptosis and Autophagy

Abstract

This study aimed to investigate the effects of the coadministration of budesonide (Bud) and the extracts of Epimedii Folium and Ligustri Lucidi Fructus (EEL) on regulating apoptosis and autophagy in asthmatic rats. Forty Sprague-Dawley rats were divided randomly into five groups (8 rats in each group): normal control (control), asthma model (asthma), Bud (1 mg Bud suspension in 50 ml sterile physiological saline for 30 min), EEL (100 mg/kg EEL), and group of coadministration of Bud and EEL (Bud&EEL, 100 mg/kg EEL plus Bud by nebulized inhalation for 30 min). Rats were sensitized and challenged with ovalbumin for 7 weeks and treated with corresponding drug for 4 weeks. We anesthetized all rats with 25% ethyl carbamate (4 ml/kg) and took lung tissues and BALF after final ovalbumin challenge to observe the lung histopathology and morphometry; apoptosis in BALF and lung tissue; protein expressions of Ki-67, α-SMA, cleaved Caspase-3, p-mTOR, and LC3; and protein and mRNA expressions of Bax, Bcl-2, Caspase-3, P53, mTOR, and Beclin-1. Results showed that Bud&EEL could alleviate airway remodeling, inhibit cell proliferation and autophagy in lung tissue, and promote apoptosis in BALF and lung tissue in ovalbumin-induced asthma rats through downregulating the protein expressions of α-SMA and Ki-67, the protein ratio of LC3-II/LC3-I and Bcl-2/Bax, and the protein and mRNA expressions of Bcl-2 and Beclin-1, while upregulating the protein expressions of cleaved Caspase-3 and p-mTOR, and the protein and mRNA expressions of Bax, Caspase-3, P53, and mTOR. Bud&EEL had better effects than single-use Bud on improving airway remodeling, promoting apoptosis, and regulating the expressions of autophagy- and apoptosis-related proteins. This study suggested that the effects of coadministration of EEL and Bud on regulating apoptosis and autophagy were better than those of single-use Bud treatment, and that might be the mechanism of attenuating airway remodeling, providing an alternative therapy for asthma.

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“…Recent evidence suggested that formononetin and calycosin, two flavonoids predominantly representing in Astragalus atropilosulus, could alleviate allergic asthma by protecting epithelial integrity via regulating and activating G protein coupled estrogen receptor (Yuan et al, 2020). For supplementary therapy, the coadministration of budesonide and the extracts of Epimedium brevicornu in asthma were better than budesonide individual treatment (Ma et al, 2020). Thus, it is considerable to treat asthma with a combination consisting of HL Granule, which was confirmed by our experiments.…”

Conciliatory Anti-Allergic Decoction Attenuates Pyroptosis in RSV-Infected Asthmatic Mice and Lipopolysaccharide (LPS)-Induced 16HBE Cells by Inhibiting TLR3/NLRP3/NF-κB/IRF3 Signaling Pathway

“…We found that CAD treatment inhibited airway cell apoptosis of lung tissues compared to the asthma mice, which was demonstrated by using TUNEL. As we have known, the Bcl-2/Bax/Cleaved caspase-3 signaling pathway has been reported in regulating cell apoptosis and survival in many diseases, including asthma [ 38 ]. Bcl-2 as an apoptosis-inhibiting protein and Bax as an apoptosis-promoting protein plays a central role in inhibiting or promoting intrinsic programmed cell death.…”

A review of botany, phytochemistry, pharmacology, and applications of the herb with the homology of medicine and food: Ligustrum lucidum W.T. Aiton

“…As a major class of chemical components in L. lucidum, these compounds have various biological activity. They have been demonstrated to prevent and treat many types of ailments such as pain, inflammation, hyperlipidemic, and hepatotoxicity as well as vision improvement effects (Liu H. et al, 2020;Wu et al, 2021). Specnuezhenide 7, one of the most abundant components and its content used as the criteria to evaluate the quality of this crude herb, has been proven to possess strong biological effects, including regulating immunity, antivirus, anti-oxidation, and hepatoprotective activities.…”