Immunosuppressive effects of the standardized extract of Zingiber zerumbet on innate immune responses in Wistar rats

Abstract

Zingiber zerumbet rhizome has been used in traditional medicine mainly for the treatment of various immune-inflammatory related ailments and has been shown to exhibit a wide spectrum of biological effects especially antioxidant and anti-inflammatory activities. The present study was aimed to investigate the immunosuppressive effects of the standardized 80% ethanol extract of Z. zerumbet at 100, 200, and 400 mg/kg on the innate immune responses in male Wistar rats. The immune parameters determined were chemotaxis of neutrophils, Mac-1 expression, engulfment of Escherichia coli by neutrophils, reactive oxygen species production, and plasma lysozyme and ceruloplasmin levels. Zerumbone was qualitatively and quantitatively determined in the extract by using a validated reversed-phase HPLC, whereas liquid chromatography tandem-mass spectrometry (LC -MS/MS) was used to profile the secondary metabolites. Z. zerumbet significantly inhibited the migration of neutrophils, expressions of CD11b/CD18 integrin, phagocytic activity, and production of reactive oxygen species in a dose-dependent manner. The extract also dose-dependently inhibited the expressions of lysozyme and ceruloplasmin in the rat plasma. Z. zerumbet extract possessed strong inhibitory effects on the innate immune responses and has potential to be developed into an effective immunosuppressive agent.

Zerumbone Protects against Carbon Tetrachloride (CCl4)-Induced Acute Liver Injury in Mice via Inhibiting Oxidative Stress and the Inflammatory Response: Involving the TLR4/NF-κB/COX-2 Pathway

“…Antioxidant enzymes, such as SOD and GSH-Px plus GSH, which are scavengers of ROS in the liver, are the first line of defense against oxidative stress-induced tissue injury [34]. Several previous studies have shown that ZER can inhibit the generation of ROS [35,36,37,38]. For instance, ZER was found to provide protection to pancreatic β cells from high glucose-induced cytotoxicity through directly interfering with ROS production [39].…”

Antitumor Potential of Immunomodulatory Natural Products

“…However, between the diterpene compounds that have been isolated from the extract, andrographolide (1), 14-deoxyandrographolide (2), and 14-deoxy-11,12-didehydroandrographolide (3), only 1 significantly inhibited the proliferation of cancer cells with GI 50 (concentration required to inhibit the 50% growth) values between 10 and 28 µM [29]. Among active terpenes, zerumbone (4, Figure 2), a sesquiterpenoidic derivative found in the rhizomes of Zingiberaceae plants, showed different pharmacological properties like antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic [30,31]. This compound exerted its antitumor activity significantly suppressing expansion and metastasis by modulating nuclear factor kappa of activated B Among active terpenes, zerumbone (4, Figure 2), a sesquiterpenoidic derivative found in the rhizomes of Zingiberaceae plants, showed different pharmacological properties like antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic [30,31].…”

“…Among active terpenes, zerumbone (4, Figure 2), a sesquiterpenoidic derivative found in the rhizomes of Zingiberaceae plants, showed different pharmacological properties like antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic [30,31]. This compound exerted its antitumor activity significantly suppressing expansion and metastasis by modulating nuclear factor kappa of activated B Among active terpenes, zerumbone (4, Figure 2), a sesquiterpenoidic derivative found in the rhizomes of Zingiberaceae plants, showed different pharmacological properties like antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic [30,31]. This compound exerted its antitumor activity significantly suppressing expansion and metastasis by modulating nuclear factor kappa of activated B cells (NF-kB), protein kinase B (PKB), interleukin 6/janus kinase 2/signal transducer, activator of transcription 3 (IL-6/JAK2/STAT3), and their downstream target proteins.…”

“…Even if a considerable quantity of investigations on biological mechanisms of macrofungi macromolecules were published, few works investigated on the anticancer and immunomodulatory effects of terpenoids isolated from this source. Triterpenoids (Figure 5) such as ganoderic acids (25), ganoderenic acids (26), ganodermic acids (27), applanoxidic acids (28), ganoderols ( 29) lucidone (30), ganodermanontriol (31), and ganodermanondiol (32) have been isolated exclusively from macrofungi and higher fungi (Basidiomycetes) [138]. These molecules show highly oxidized lanostane structures with anti-infectives, cytotoxic, and immunomodulatory activities [100].…”

Bioactive Compounds from Zingiber montanum and Their Pharmacological Activities with Focus on Zerumbone

“…In vivo Male wistar rats ZER inhibited the migration of neutrophils, expressions of CD11b/CD18 integrin, phagocytic activity, and production of reactive oxygen species [162] In vitro CD18 integrin expression and phagocytic engulfment ZER showed strong inhibition on the phagocytosis of neutrophils.Z [163] In vitro Asthmatic mouse model ZER reduced ovalbumin (OVA)-specific immunoglobulin E (IgE) and induced IgG2a antibody production. It also reduced the production of eotaxin, keratinocyte-derived chemokine (KC), IL-4, IL-5, IL-10, and IL-13, and promoted Th1 cytokine interferon (IFN)-γ production.…”