Anti-Inflammatory and Immune Regulatory Actions of Naja naja atra Venom

Wang, Shuzhi; Qin, Zheng‐Hong

doi:10.3390/toxins10030100

Cited by 15 publications

(10 citation statements)

References 102 publications

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“…In addition, bee venom contains PLA2, melittin and hyaluronidases, among other factors. Bee venom is useful in decreasing serum levels of rheumatoid factor, PCR, anti-streptolysin O and proinflammatory cytokines such as TNF-α, IFN-γ, IL-6 and IL-1β [ 79 , 86 ]. The excretion of hydroxyproline and glucosamine in urine, as well as serum levels of acid phosphatase and alkaline phosphatase, was also decreased in RA models treated with Naja kouthia venom, indicating the protective and anti-inflammatory effect on cartilage degeneration and destruction [ 87 ].…”

Section: Effects On Innate Immunitymentioning

confidence: 99%

Biological Effects of Animal Venoms on the Human Immune System

Avalo

Barrera

Agudelo-Delgado

et al. 2022

Toxins

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Venoms are products of specialized glands and serve many living organisms to immobilize and kill prey, start digestive processes and act as a defense mechanism. Venoms affect different cells, cellular structures and tissues, such as skin, nervous, hematological, digestive, excretory and immune systems, as well as the heart, among other structures. Components of both the innate and adaptive immune systems can be stimulated or suppressed. Studying the effects on the cells and molecules produced by the immune system has been useful in many biomedical fields. The effects of venoms can be the basis for research and development of therapeutic protocols useful in the modulation of the immunological system, including different autoimmune diseases. This review focuses on the understanding of biological effects of diverse venom on the human immune system and how some of their components can be useful for the study and development of immunomodulatory drugs.

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Section: Effects On Innate Immunitymentioning

confidence: 99%

Biological Effects of Animal Venoms on the Human Immune System

Avalo

Barrera

Agudelo-Delgado

et al. 2022

Toxins

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“…A particularly broad and complex venom-induced inflammatory response is seen after cobra envenoming, with both pro-and anti-inflammatory components [89]. Naja annulifera venom triggers acute systemic inflammation, including PLA 2 -dependent neutrophilia and increased plasma levels of IL-6 and MCP-1.…”

Section: Inflammation and Inflammation-mediatedmentioning

confidence: 99%

Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways

Bickler

2020

Toxins

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The active components of snake venoms encompass a complex and variable mixture of proteins that produce a diverse, but largely stereotypical, range of pharmacologic effects and toxicities. Venom protein diversity and host susceptibilities determine the relative contributions of five main pathologies: neuromuscular dysfunction, inflammation, coagulopathy, cell/organ injury, and disruption of homeostatic mechanisms of normal physiology. In this review, we describe how snakebite is not only a condition mediated directly by venom, but by the amplification of signals dysregulating inflammation, coagulation, neurotransmission, and cell survival. Although venom proteins are diverse, the majority of important pathologic events following envenoming follow from a small group of enzyme-like activities and the actions of small toxic peptides. This review focuses on two of the most important enzymatic activities: snake venom phospholipases (svPLA2) and snake venom metalloproteases (svMP). These two enzyme classes are adept at enabling venom to recruit homologous endogenous signaling systems with sufficient magnitude and duration to produce and amplify cell injury beyond what would be expected from the direct impact of a whole venom dose. This magnification produces many of the most acutely important consequences of envenoming as well as chronic sequelae. Snake venom PLA2s and MPs enzymes recruit prey analogs of similar activity. The transduction mechanisms that recruit endogenous responses include arachidonic acid, intracellular calcium, cytokines, bioactive peptides, and possibly dimerization of venom and prey protein homologs. Despite years of investigation, the precise mechanism of svPLA2-induced neuromuscular paralysis remains incomplete. Based on recent studies, paralysis results from a self-amplifying cycle of endogenous PLA2 activation, arachidonic acid, increases in intracellular Ca2+ and nicotinic receptor deactivation. When prolonged, synaptic suppression supports the degeneration of the synapse. Interaction between endothelium-damaging MPs, sPLA2s and hyaluronidases enhance venom spread, accentuating venom-induced neurotoxicity, inflammation, coagulopathy and tissue injury. Improving snakebite treatment requires new tools to understand direct and indirect effects of envenoming. Homologous PLA2 and MP activities in both venoms and prey/snakebite victim provide molecular targets for non-antibody, small molecule agents for dissecting mechanisms of venom toxicity. Importantly, these tools enable the separation of venom-specific and prey-specific pathological responses to venom.

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“…Its analgesic potency is much higher than that of morphine and it has no addictive effect, however, its effect is slow. It has been approved for the treatment of chronic pain such as intractable neuralgia and cancer pain [ 4 ]. Resveratrol (Res) is a natural stilbene compound extracted from plants, It has been shown to have a definite central analgesic effect, [ 5 – 7 ] which is quick but transient.…”

Section: Introductionmentioning

confidence: 99%

pH-sensitive dual drug loaded janus nanoparticles by oral delivery for multimodal analgesia

et al. 2021

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Background Based on the concept of “multimodal analgesia”, a novel dual drug delivery system was designed to achieve synergistic analgesia between najanajaatra venom protein (αCT) and resveratrol (Res). In order to meet the joint loading of two drugs with different physicochemical properties without affecting each other, an oral Janus nanoparticle (JNP) with a unique cavity structure and synergistic drug delivery was constructed using an improved double emulsion solvent evaporation method, and combined with low-molecular-weight chitosan/sodium alginate and PLGA to achieve its pH-responsive. Results The synthesized αCT/Res-JNPs are homogeneous in shape, with a two-compartment structure, approximately 230 nm in size, and zeta potential of 23.6 mV. Drug release assayed in vitro show that JNP was stable in simulated gastric juice (pH = 1.2) but was released in phosphate buffer saline (pH = 7.4). After intragastric administration in rats, PK evaluation showed that αCT/Res-JNPs could significantly improve the oral bioavailability, and the simultaneous encapsulation of the two drugs had no significant interaction on PK parameters. An obvious synergistic analgesic effects of αCT/Res-JNPs was confirmed in a spinal cord injury and acute pain model. Confocal laser scanning microscopy and single-pass intestinal perfusion model provided strong evidence that αCT/Res-JNPs could pass through intestinal epithelial cells, and the endocytosis pathway was mainly involved in the mediation and pinocytosis of reticulin. The concentrations of αCT and Res from αCT/Res-JNP in lymphatic transport were only about 8.72% and 6.08% of their blood concentrations at 1 h, respectively, which indicated that lymphatic transport in the form of JNP has limited advantages in improving the oral bioavailability of Res and αCT. Cellular uptake efficiency at 4 h was about 10–15% in Caco-2 cell lines for αCT/Res-JNP, but was reduced to 7% in Caco-2/HT29-MTX co-culture models due to the hindrance by the mucus layers. Approximately 12–17% of αCT/Res-JNP were transported across Caco-2/HT29-MTX/Raji monolayers. The cumulative absorption of JNP in three cell models was higher than that of free drug. Conclusions This study investigated the contribution of Janus nanoparticles in oral absorption, and provide a new perspective for oral administration and analgesic treatment of dual drug delivery system containing peptide drugs. Graphic Abstract

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Anti-Inflammatory and Immune Regulatory Actions of Naja naja atra Venom

Cited by 15 publications

References 102 publications

Biological Effects of Animal Venoms on the Human Immune System

Biological Effects of Animal Venoms on the Human Immune System

Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways

pH-sensitive dual drug loaded janus nanoparticles by oral delivery for multimodal analgesia

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