Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.
Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; Humans ; Prospective Studies ; SARS-CoV-2 ; Vasoactive Intestinal Peptide/therapeutic use* ; Zika Virus ; Zika Virus Infection/drug therapy*

OBJECTIVETo observe effects of treatment from the lung and treatment from the intestine on the level of vasoactive intestinal peptide (VIP) in the lung and intestine of ulcerative colitis (UC) rats.

METHODSThe UC rat model was established in 52 rats by using rabbit intestine mucosa tissue allergen combined TNBS-ethanol model (with the model successful rate of 78.0%). Eight rats randomly selected from 40 successfully modeled rats and 8 of 16 rats from the normal group were recruited as the model group and the normal control group before intervention (at week 0). The rest 32 successfully modeled rats were randomly divided into the model group, the Western medicine treatment group (salazosulfapyridine), the treatment from lung group (Huangqi Jiegeng Decoction), and the treatment from intestine group (Huangqi Huanglian Decoction), 8 in each group. Rats in each treatment group were administered with corresponding medication 8 times the dose of a 60 kg adult human. Another 8 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the model group and the normal group by gastrog avage, once per day. Contents of VIP in the lung tissue and the intestinal tissue were detected at week 0 and 4 after 4-week consecutive intervention. Pathomorphological changes of the lung tissue and the colon tissue were observed under light microscope.

RESULTSCompared with the normal control group at week 0, evenly distributed diffuse inflammation could be seen in the pulmonary interstitial tissue; the bronchial wall was thickened; a huge amount of infiltration surrounded bronchi and blood vessels; a large area of necrosis of intestinal mucosa and inflammatory cell infiltration could also be seen in the model group. Pathological injuries of the lung and the colon were more alleviated in each treatment group than in the model group at the same time point. Compared with the normal control group at the same time point, VIP contents in the lung tissue significantly decreased in the model group at the end of week 4 (P<0.05); VIP contents in the colon tissue significantly increased in the model group at the end of week 0 and 4 (P <0.05). Compared with the model group, VIP contents in the lung tissue significantly increased in the Western medicine treatment group and the treatment from lung group at the end of week 4 (P<0.01); VIP contents in the colon tissue significantly decreased in the treatment from lung group and the treatment from intestine group (P<0.05, P<0.01).

CONCLUSIONTreatment from the lung and treatment from the intestine showed predominant advantage in improving local inflammation of the lung and the intestinal tract, alleviating pathological injuries, promoting repair of injuries through regulating VIP contents in the lung tissue and the colon tissue.

Animals ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; Lung ; Male ; Rabbits ; Rats ; Vasoactive Intestinal Peptide

OBJECTIVETo investigate the therapeutical effect of recombinant plasmid containing vasoactive intestinal peptide gene (pcDNA3.1+/VIP) on collagen-induced arthritis (CIA) in rats.

METHODSThe experimental arthritis was induced by intradermal injection of bovine type II collagen emulsified in Freund's adjuvants in male SD rats. The rats then were given intra-articular injection with recombinant plasmid (pcDNA3.1+/VIP). The levels of serum TNF-alpha, IL-4 and IL-2 were detected by Avidin-Biotin Peroxdase Complex-enzyme-linked immunosorbent assay (ABC-ELISA) and the pathological changes in the joint of rats were observed.

RESULTHistological examination showed massive inflammatory infiltration in the joint with destruction of bone and cartilage, while the severity of pathological changes in synovia of VIP-treated rats was markedly reduced. Compared with normal group, the serum TNF-alpha, IL-2 levels of CIA rats were significantly increased (P <0.05) and IL-4 level was decreased (P<0.05). Compared with control and pcDNA3.1+ -treated CIA rats, serum TNF-alpha and IL-2 levels of pcDNA3.1+/VIP-treated rats were decreased and IL-4 level was increased (P<0.05).

CONCLUSIONRecombinant plasmid containing vasoactive intestinal peptide gene (pcDNA3.1+/VIP) can reduce the clinical and histological severity of established CIA and it might be a promising candidate for treatment of rheumatoid arthritis.

Animals ; Arthritis, Experimental ; therapy ; Arthritis, Rheumatoid ; therapy ; Genetic Therapy ; Injections, Intra-Articular ; Male ; Plasmids ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; therapeutic use ; Vasoactive Intestinal Peptide ; biosynthesis ; genetics ; therapeutic use

OBJECTIVETo investigate the protective effects of vasoactive intestinal peptide (VIP) on septic shock rats and explore its possible mechanism.

METHODSCecal ligation and puncture (CLP) was performed to produce septic shock rat model. Thirty adult Sprague-dawley rats were randomly divided into 3 groups with 10 animals in each group: sham operation group, CLP group and VIP group. The rats in VIP group were given intravenous injection of VIP (5 nmol per rat) instantly after the CLP operation. Then the mean arterial pressure (MAP) was monitored consistently and survival rate was observed. Blood samples were obtained from femoral artery for measuring the serum concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) by using enzyme-linked immunosorbent assays (ELISA). Organs (lung, kidney and intestine) were harvested for pathological examination.

RESULTSAt each time point after 8 h, the MAP of VIP rats was significantly higher than that in CLP rats (P<0.05). In VIP group rats, the serum TNF-alpha concentration was decreased meanwhile IL-10 level was increased with markedly alleviated organic pathological injuries and the survival rate was obviously raised.

CONCLUSIONSVIP exerts protective effects on septic shock rats through inhibiting production of proinflammatory factors and stimulating the production of anti-inflammatory cytokines.

Animals ; Blood Pressure ; drug effects ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Interleukin-10 ; blood ; Male ; Neuroprotective Agents ; administration & dosage ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; blood ; mortality ; prevention & control ; Survival Rate ; Tumor Necrosis Factor-alpha ; metabolism ; Vasoactive Intestinal Peptide ; administration & dosage ; therapeutic use

To observe the effect of vasoactive intestinal peptide (VIP) on the metabolism of intestinal fluid and cyclic AMP protein kinase A signaling pathway (cAMP-PKA) and water channel protein 3 (AQP3) in rats with constipation, and to explore the mechanism of VIP in the treatment of constipation.
 Methods: A total of 45 healthy adult rats were randomly divided into a control group, a model group, a model +VIP group. After 4 weeks of VIP treatment, the first black stool time were examined with the ink gastric method; the water content in feces was calculated; the morphological changes in colonic tissues were observed by HE staining. The expression of VIP and AQP3 protein levels in colon tissues were detected by Western blot; and the cAMP, PKA, AQP3 mRNA expression levels were detected by quantitative real time polymerase chain reaction (qPCR). 
 Results: Compared with the control group, the first black stool time was prolonged, the water content of fecal decreased significantly (both P<0.01); part of the colon mucosa epithelial cells were destructed; the goblet cell volume decreased and quantity was reduced; the contents of AQP3 and VIP in colon tissues were significantly decreased, and the cAMP, PKA and AQP3 mRNA levels were decreased in the model group (all P<0.05). Compared with the model group, the first black stool time in the model +VIP group was shortened, the fecal water content increased significantly (both P<0.05); the mucosal epithelium integrity improved, the number of goblet cells increased; the content of AQP3 and VIP in colon tissues was increased, and the cAMP, PKA, and AQP3 mRNA levels were elevated (all P<0.05).
 Conclusion: Intravenous injection of VIP can regulate intestinal fluid metabolism and improve the symptoms of constipation in rats, which might be related to the regulation of VIP-cAMP-PKA-AQP3 signaling pathway.
Animals ; Aquaporin 3 ; physiology ; Aquaporins ; Blotting, Western ; Colon ; chemistry ; pathology ; Constipation ; physiopathology ; therapy ; Cyclic AMP ; physiology ; Defecation ; Epithelial Cells ; pathology ; Feces ; chemistry ; Goblet Cells ; pathology ; Intestinal Mucosa ; metabolism ; pathology ; RNA, Messenger ; Rats ; Signal Transduction ; Vasoactive Intestinal Peptide ; administration & dosage ; physiology ; therapeutic use

OBJECTIVETo investigate the effects of vasoactive intestinal peptide (VIP) on the airway inflammation and its regulatory effect on Th17/Treg imbalance in asthmatic mice.

METHODSA total of 30 BALB/c mice were equally and randomly divided into three groups: control, asthma, and VIP. An acute asthmatic mouse model was established by sensitization and challenge with ovalbumin (OVA). The control group received normal saline instead of OVA. Before the challenge with OVA, the VIP group was administered VIP (20 μg/mL) by aerosol inhalation for 30 minutes. The bronchoalveolar lavage fluid (BALF) and the lung tissue were collected from mice. The pathological changes in the lung tissue were observed by hematoxylin and eosin staining. The levels of Th17/Treg-related cytokines in BALF were measured by enzyme-linked immunosorbent assay. The expression of retinoid-related orphan receptor gamma t (RORγt) and forkhead box P3 (Foxp3) were measured by real-time fluorescence quantitative PCR and immunohistochemistry.

RESULTSThe histopathological results showed that the VIP group had milder symptoms of airway inflammation than the asthma group. The level of IL-17 in BALF in the asthma group was significantly higher than that in the control group and the VIP group (P<0.01), but the level of IL-17 in the control group was significantly lower than that in the VIP group (P<0.01). The level of IL-10 in BALF in the asthma group was significantly lower than that in the control group and the VIP group (P<0.01, but the level of IL-10 in the VIP group was significantly higher than that in the control group (P<0.01). The asthma group showed significantly higher expression levels of RORγt mRNA and protein in the lung tissue and significantly lower expression levels of Foxp3 mRNA and protein than the control group (P<0.01). The VIP group had significantly lower expression levels of RORγt mRNA and protein in the lung tissue and significantly higher expression levels of Foxp3 mRNA and protein than the asthma group (P<0.05).

CONCLUSIONSThe Th17/Treg imbalance may be closely related to the airway inflammation in asthmatic mice. VIP can improve airway inflammation by regulating the Th17/Treg imbalance in asthmatic mice.

Animals ; Asthma ; drug therapy ; immunology ; Forkhead Transcription Factors ; genetics ; Interleukin-10 ; analysis ; Interleukin-17 ; analysis ; Male ; Mice ; Mice, Inbred BALB C ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; genetics ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology ; Vasoactive Intestinal Peptide ; pharmacology ; therapeutic use