Effect of a chemical chaperone, tauroursodeoxycholic acid, on HDM-induced allergic airway disease.

Endoplasmic reticulum (ER) stress-induced unfolded protein response plays a critical role in inflammatory diseases, including allergic airway disease. However, the benefits of inhibiting ER stress in the treatment of allergic airway disease are not well known. Herein, we tested the therapeutic potential of a chemical chaperone, tauroursodeoxycholic acid (TUDCA), in combating allergic asthma, using a mouse model of house dust mite (HDM)-induced allergic airway disease. TUDCA was administered during the HDM-challenge phase (preventive regimen), after the HDM-challenge phase (therapeutic regimen), or therapeutically during a subsequent HDM rechallenge (rechallenge regimen). In the preventive regimen, TUDCA significantly decreased HDM-induced inflammation, markers of ER stress, airway hyperresponsiveness (AHR), and fibrosis. Similarly, in the therapeutic regimen, TUDCA administration efficiently decreased HDM-induced airway inflammation, mucus metaplasia, ER stress markers, and AHR, but not airway remodeling. Interestingly, TUDCA administered therapeutically in the HDM rechallenge regimen markedly attenuated HDM-induced airway inflammation, mucus metaplasia, ER stress markers, methacholine-induced AHR, and airway fibrotic remodeling. These results indicate that the inhibition of ER stress in the lungs through the administration of chemical chaperones could be a valuable strategy in the treatment of allergic airway diseases.

Phytochemical screening and evaluation of in vitro angiotensin-converting enzyme inhibitory activity of Artocarpus altilis leaf.

This study investigates the effect of Artocarpus altilis leaf extracts on angiotensin-converting enzyme (ACE) activity. Among the extracts tested, hot ethanol extract exhibited a potent ACE-inhibitory activity with an IC50 value of 54.08 ± 0.29 µg mL⁻¹ followed by cold ethyl acetate extract (IC50 of 85.44 ± 0.85 µg mL⁻¹). In contrast, the hot aqueous extracts showed minimum inhibition with the IC50 value of 765.52 ± 11.97 µg mL⁻¹ at the maximum concentration tested. Further, the phytochemical analysis indicated the varied distribution of tannins, phenolics, glycosides, saponins, steroids, terpenoids and anthraquinones in cold and hot leaf extracts. The correlation between the phytochemical analysis and ACE-inhibitory activity suggests that the high content of glycosidic and phenolic compounds could be involved in exerting ACE-inhibitory activity. In conclusion, this study supports the utilisation of A. altilis leaf in the folk medicine for the better treatment of hypertension. Further studies on isolation and characterisation of specific ACE-inhibitory molecule(s) from ethyl acetate, ethanol and methanol extracts of A. altilis leaf would be highly interesting.

Radical scavenging and angiotensin converting enzyme inhibitory activities of standardized extracts of Ficus racemosa stem bark.

The present study evaluated the radical scavenging and angiotensin converting enzyme (ACE) inhibitory activity of cold and hot aqueous extracts of Ficus racemosa (Moraceae) stem bark. The extracts were standardized using HPLC. Radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl radical and angiotensin converting enzyme inhibitory activity using rabbit lung and partially purified porcine kidney ACE. HPLC profiles of cold aqueous extract (FRC) showed the presence of bergenin, an isocoumarin, while hot aqueous extract (FRH) was found to contain ferulic acid, kaempferol and coumarin in addition to bergenin. FRH showed significantly higher (p ≤ 0.01) radical scavenging activity than FRC and butylated hydroxytoluene (BHT), consequently resulting in a significantly lower (p ≤ 0.01) IC50 value than FRC and BHT. Both the extracts exhibited a dose dependent inhibition of porcine kidney and rabbit lung ACE. FRH showed significantly higher (p ≤ 0.01) activity than FRC with lower IC(50) values of 1.36 and 1.91 µg/mL respectively, for porcine kidney and rabbit lung ACE, compared with those of FRC (128 and 291 µg/mL). Further, a significant correlation (r = 0.893; p ≤ 0.05) was observed between radical scavenging activity and ACE-inhibitory activity. This is the first report on the ACE-inhibitory activity of F. racemosa stem bark suggesting its potential to be utilized as a therapeutic alternative for hypertension.