Anti-inflammatory effects of Perilla frutescens in activated human neutrophils through two independent pathways: Src family kinases and Calcium

Abstract

The leaves of Perilla frutescens (L.) Britt. have been traditionally used as an herbal medicine in East Asian countries to treat a variety diseases. In this present study, we investigated the inhibitory effects of P. frutescens extract (PFE) on N-formyl-Met-Leu-Phe (fMLF)-stimulated human neutrophils and the underlying mechanisms. PFE (1, 3, and 10 μg/ml) inhibited superoxide anion production, elastase release, reactive oxygen species formation, CD11b expression, and cell migration in fMLF-activated human neutrophils in dose-dependent manners. PFE inhibited fMLF-induced phosphorylation of the Src family kinases (SFKs), Src (Tyr416) and Lyn (Tyr396), and reduced their enzymatic activities. Both PFE and PP2 (a selective inhibitor of SFKs) reduced the phosphorylation of Burton’s tyrosine kinases (Tyr223) and Vav (Tyr174) in fMLF-activated human neutrophils. Additionally, PFE decreased intracellular Ca2+ levels ([Ca2+]i), whereas PP2 prolonged the time required for [Ca2+]i to return to its basal level. Our findings indicated that PFE effectively regulated the inflammatory activities of fMLF-activated human neutrophils. The anti-inflammatory effects of PFE on activated human neutrophils were mediated through two independent signaling pathways involving SFKs (Src and Lyn) and mobilization of intracellular Ca2+.

Imidazole alkaloids inhibit the pro-inflammatory mechanisms of human neutrophil and exhibit anti-inflammatory properties in vivo

“…The increase in intracellular calcium plays an important role in several functions in a variety of cell types, including neutrophils, for example, activating calcium‐dependent events, such as PKC activation . Our study demonstrated that EPI and EPIIS reduced the prolonged increase in calcium mobilization into the cytosolic compartment after activation of neutrophils with fMLP.…”

“…The modulation of this system could attenuate the inflammatory reactions because of HOCl, the most powerful oxidant produced by human neutrophils, with the potential to cause considerable tissue damage in many inflammatory diseases. [29] The increase in intracellular calcium plays an important role in several functions in a variety of cell types, including neutrophils, [30] for example, activating calcium-dependent events, such as PKC activation. [3] Our study demonstrated that EPI and EPIIS reduced the prolonged increase in calcium mobilization into the cytosolic compartment after activation of neutrophils with fMLP.…”

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“…Upon activation, neutrophils release antimicrobial proteins in a process referred to as degranulation. Elastase release was measured spectrophotometrically using a synthetic elastase substrate, methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide 19,20. Human neutrophils suspensions (6×10 5 cells/mL) were preincubated in HBSS containing CaCl 2 (1 mM) and elastase substrate (0.1 mM) at 37 °C.…”

Discovery and analysis the anti-pseudo-allergic components from Perilla frutescens leaves by overexpressed MRGPRX2 cell membrane chromatography coupled with HPLC-ESI-IT-TOF system

“…Perilla frutescens (PF) is a common herb which has been widely used as traditional Chinese food and medicine . It has been reported that P. frutescens has good pharmacological activities such as allergy relief, anti‐inflammatory, anti‐oxidation and asthma therapy . The main effective components from different parts of PF mainly contained phenolic compounds, flavonoids and triterpenes .…”