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Fulltext A Review of Malaysian Herbal Plants and Their Active Constituents with Potential Therapeutic Applications in Sepsis

Liew KY, Hafiz MF, Chong YJ, Harith HH, Israf DA, Tham CL

Evid Based Complement Alternat Med, 2020;2020:8257817.
PMID: 33193799 DOI: 10.1155/2020/8257817

Sepsis refers to organ failure due to uncontrolled body immune responses towards infection. The systemic inflammatory response triggered by pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) from Gram-negative bacteria, is accompanied by the release of various proinflammatory mediators that can lead to organ damage. The progression to septic shock is even more life-threatening due to hypotension. Thus, sepsis is a leading cause of death and morbidity globally. However, current therapies are mainly symptomatic treatment and rely on the use of antibiotics. The lack of a specific treatment demands exploration of new drugs. Malaysian herbal plants have a long history of usage for medicinal purposes. A total of 64 Malaysian plants commonly used in the herbal industry have been published in Malaysian Herbal Monograph 2015 and Globinmed website (http://www.globinmed.com/). An extensive bibliographic search in databases such as PubMed, ScienceDirect, and Scopus revealed that seven of these plants have antisepsis properties, as evidenced by the therapeutic effect of their extracts or isolated compounds against sepsis-associated inflammatory responses or conditions in in vitro or/and in vivo studies. These include Andrographis paniculata, Zingiber officinale, Curcuma longa, Piper nigrum, Syzygium aromaticum, Momordica charantia, and Centella asiatica. Among these, Z. officinale is the most widely studied plant and seems to have the highest potential for future therapeutic applications in sepsis. Although both extracts as well as active constituents from these herbal plants have demonstrated potential antisepsis activity, the activity might be primarily contributed by the active constituent(s) from each of these plants, which are andrographolide (A. paniculata), 6-gingerol and zingerone (Z. officinale), curcumin (C. longa), piperine and pellitorine (P. nigrum), biflorin (S. aromaticum), and asiaticoside, asiatic acid, and madecassoside (C. asiatica). These active constituents have shown great antisepsis effects, and further investigations into their clinical therapeutic potential may be worthwhile.

Matched MeSH terms: Pathogen-Associated Molecular Pattern Molecules
Toll-like Receptor as a Molecular Link between Metabolic Syndrome and Inflammation: A Review

Wong SK, Chin KY, Ima-Nirwana S

Curr Drug Targets, 2019;20(12):1264-1280.
PMID: 30961493 DOI: 10.2174/1389450120666190405172524

Metabolic Syndrome (MetS) involves a cluster of five conditions, i.e. obesity, hyperglycaemia, hypertension, hypertriglyceridemia and low High-Density Lipoprotein (HDL) cholesterol. All components of MetS share an underlying chronic inflammatory aetiology, manifested by increased levels of pro-inflammatory cytokines. The pathogenic role of inflammation in the development of MetS suggested that toll-like receptor (TLR) activation may trigger MetS. This review summarises the supporting evidence on the interactions between MetS and TLR activation, bridged by the elevation of TLR ligands during MetS. The regulatory circuits mediated by TLR activation, which modulates signal propagation, leading to the state of chronic inflammation, are also discussed. Taken together, TLR activation could be the molecular basis in the development of MetS-induced inflammation.

Matched MeSH terms: Pathogen-Associated Molecular Pattern Molecules/metabolism
Toward understanding of rice innate immunity against Magnaporthe oryzae

Azizi P, Rafii MY, Abdullah SN, Nejat N, Maziah M, Hanafi MM, et al.

Crit Rev Biotechnol, 2016;36(1):165-74.
PMID: 25198435 DOI: 10.3109/07388551.2014.946883

The blast fungus, Magnaporthe oryzae, causes serious disease on a wide variety of grasses including rice, wheat and barley. The recognition of pathogens is an amazing ability of plants including strategies for displacing virulence effectors through the adaption of both conserved and variable pathogen elicitors. The pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) were reported as two main innate immune responses in plants, where PTI gives basal resistance and ETI confers durable resistance. The PTI consists of extracellular surface receptors that are able to recognize PAMPs. PAMPs detect microbial features such as fungal chitin that complete a vital function during the organism's life. In contrast, ETI is mediated by intracellular receptor molecules containing nucleotide-binding (NB) and leucine rich repeat (LRR) domains that specifically recognize effector proteins produced by the pathogen. To enhance crop resistance, understanding the host resistance mechanisms against pathogen infection strategies and having a deeper knowledge of innate immunity system are essential. This review summarizes the recent advances on the molecular mechanism of innate immunity systems of rice against M. oryzae. The discussion will be centered on the latest success reported in plant-pathogen interactions and integrated defense responses in rice.

Matched MeSH terms: Pathogen-Associated Molecular Pattern Molecules
Differential transcriptome analysis of the disease tolerant Madagascar-Malaysia crossbred black tiger shrimp, Penaeus monodon hepatopancreas in response to acute hepatopancreatic necrosis disease (AHPND) infection: inference on immune gene response and interaction

Soo TCC, Devadas S, Mohamed Din MS, Bhassu S

Gut Pathog, 2019;11:39.
PMID: 31372182 DOI: 10.1186/s13099-019-0319-4

Background: Penaeus monodon is the second most widely cultured marine shrimp species in the global shrimp aquaculture industry. However, the growth of P. monodon production has been constantly impaired by disease outbreaks. Recently, there is a lethal bacterial infection, known as acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus AHPND strain (VpAHPND), which led to mass mortalities in P. monodon. Unfortunately, there is still insufficient knowledge about the underlying immune response of P. monodon upon AHPND infection. The present study aims to provide an insight into the antibacterial immune response elicited by P. monodon hepatopancreas towards AHPND infection.
Methods: We have employed high-throughput RNA-Seq technology to uncover the transcriptome changes of P. monodon hepatopancreas when challenged with VpAHPND. The shrimps were challenged with VpAHPND through immersion method with dissected hepatopancreas samples for the control group (APm-CTL) and treatment group at 3 (APm-T3), 6 (APm-T6), and 24 (APm-T24) hours post-AHPND infection sent for RNA-Seq. The transcriptome de novo assembly and Unigene expression determination were conducted using Trinity, Tgicl, Bowtie2, and RSEM software. The differentially expressed transcripts were functionally annotated mainly through COG, GO, and KEGG databases.
Results: The sequencing reads generated were filtered to obtain 312.77 Mb clean reads and assembled into 48662 Unigenes. Based on the DEGs pattern identified, it is inferred that the PAMPs carried by VpAHPND or associated toxins are capable of activating PRRs, which leads to subsequent pathway activation, transcriptional modification, and antibacterial responses (Phagocytosis, AMPs, proPO system). DAMPs are released in response to cell stress or damage to further activate the sequential immune responses. The comprehensive interactions between VpAHPND, chitin, GbpA, mucin, chitinase, and chitin deacetylase were postulated to be involved in bacterial colonization or antibacterial response.
Conclusions: The outcomes of this research correlate the different stages of P. monodon immune response to different time points of AHPND infection. This finding supports the development of biomarkers for the detection of early stages of VpAHPND colonization in P. monodon through host immune expression changes. The potential genes to be utilized as biomarkers include but not limited to C-type lectin, HMGB1, IMD, ALF, serine proteinase, and DSCAM.

Matched MeSH terms: Pathogen-Associated Molecular Pattern Molecules
Staphylococcal infections and infertility: mechanisms and management

Dutta S, Sengupta P, Izuka E, Menuba I, Jegasothy R, Nwagha U

Mol Cell Biochem, 2020 Nov;474(1-2):57-72.
PMID: 32691256 DOI: 10.1007/s11010-020-03833-4

Infertility is a subject of worldwide concern as it affects approximately 15% of couples. Among the prime contributors of infertility, urogenital bacterial infections have lately gained much clinical importance. Staphylococcal species are commensal bacteria and major human pathogens mediating an array of reproductive tract infections. Emerging evidences are 'bit by bit' revealing the mechanisms by which Staphylococci strategically disrupt normal reproductive functions. Staphylococcal species can directly or through hematogenous routes can invade the reproductive tissues. In the testicular cells, epididymis as well as in various compartments of female reproductive tracts, the pathogen recognition receptors, toll-like receptors (TLRs), can recognize the pathogen-associated molecular patterns on the Staphylococci and thereby activate inflammatory signalling pathways. These elicit pro-inflammatory mediators trigger other immune cells to infiltrate and release further inflammatory agents and reactive oxygen species (ROS). Adaptive immune responses may intensify the inflammation-induced reproductive tissue damage, particularly via activation of T-helper (Th) cells, Th1 and Th17 by the innate components or by staphylococcal exotoxins. Staphylococcal surface factors binding with sperm membrane proteins can directly impair sperm functions. Although Staphylococci, being one of the most virulent bacterial species, are major contributors in infection-induced infertility in both males and females, the mechanisms of their operations remain under-discussed. The present review aims to provide a comprehensive perception of the possible mechanisms of staphylococcal infection-induced male and female infertility and aid potential interventions to address the lack of competent therapeutic measures for staphylococcal infection-induced infertility.

Matched MeSH terms: Pathogen-Associated Molecular Pattern Molecules
Hot water extract of Pleurotus pulmonarius stalk waste enhances innate immune response and immune-related gene expression in red hybrid tilapia Oreochromis sp. following challenge with pathogen-associated molecular patterns

Ching JJ, Shuib AS, Abdullah N, Majid NA, Taufek NM, Sutra J, et al.

Fish Shellfish Immunol, 2021 Sep;116:61-73.
PMID: 34157396 DOI: 10.1016/j.fsi.2021.06.005

In aquaculture, commercial fish such as red hybrid tilapia are usually raised at high density to boost the production within a short period of time. This overcrowded environment, however, may cause stress to the cultured fish and increase susceptibility to infectious diseases. Antibiotics and chemotherapeutics are used by fish farmers to overcome these challenges, but this may increase the production cost. Studies have reported on the potential of mushroom polysaccharides that can act as immunostimulants to enhance the immune response and disease resistance in fish. In the current study, hot water extract (HWE) from mushroom stalk waste (MSW) was used to formulate fish feed and hence administered to red hybrid tilapia to observe the activation of immune system. Upon 30 days of feeding, the fish were challenged with pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (poly (I:C)) to mimic bacterial and viral infection, respectively. HWE supplementation promoted better feed utilisation in red hybrid tilapia although it did not increase the body weight gain and specific growth rate compared to the control diet. The innate immunological parameters such as phagocytic activity and respiratory burst activity were significantly higher in HWE-supplemented group than that of the control group following PAMPs challenges. HWE-supplemented diet also resulted in higher mRNA transcription of il1b and tnfa in midgut, spleen and head kidney at 1-day post PAMPs injection. Tlr3 exhibited the highest upregulation in the HWE fed fish injected with poly (I:C). At 3-days post PAMPs injection, both ighm and tcrb expression were upregulated significantly in the spleen and head kidney. Results showed that HWE supplementation enhances the immune responses of red hybrid tilapia and induced a higher serum bactericidal activity against S. agalactiae.

Matched MeSH terms: Pathogen-Associated Molecular Pattern Molecules/pharmacology*