Pharmacological effects of bioactive agents in earthworm extract:A comprehensive review

This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Comparative study of anti-inflammatory effects of different processed products through the COX-2/PGE2 signaling pathway: based on network pharmacology and molecular docking

Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.

New innovation of moisturizers containing non-steroidal anti-inflammatory agents for atopic dermatitis

Atopic dermatitis is a chronic, relapsing and extremely pruritic eczematous disease which commonly affects children. The standard management consists of a combination of anti-inflammatory drugs in adjunctive with skin care management particular moisturizer application. A concern for the side effects associated with long term use of corticosteroids has also been considered. There has been an emerging interest in moisturizer containing non-steroidal anti-inflammatory agents such as herbal extracts, vitamins, mineral and lipids. The in vitro and the in vivo studies of each agent were reviewed. The clinical study on the efficacy of moisturizers containing these agents were also demonstrated including the author's studies and clinicalexperience. These moisturizers might be considered as an alternative treatment in acute flare of mild to moderate atopic dermatitis.

Pharmacology of tetrandrine and its therapeutic use in digestive diseases

INTRODUCTIONTetrandrine (Tet) is a dibenzylisoquinoline alkaloid isolatedfrom Stephania tetrandra S. Moore, a Chinese herbalmedicine. In the past decade, lots of studies demonstrated that Tet has multiple bioactivities, It is promising to use Tet as an antifibrogenetic in liver or lung fibrosis with or without portal or pulmonary hypertension, as well as an immunomodulating and anticarcinoma drug.

Mechanisms Underlying the Anti-Inflammatory, Anti-Pruritic, and Anti-Allergic Effects of the Fuyanjie Chinese Herbal Formula : Insights from Network Pharmacology

[Objectives] To examine the mechanisms underlying the anti-inflammatory, anti-pruritic, and anti-allergic effects of the Fuyanjie Chinese herbal formula, which comprises Radix Sophorae Flavescentis, Stemonae Radix, Fructus Cnidii, and Phellodendri Chinensis Cortex, on sensitive skin using network pharmacology.[Methods] The TCMSP database was employed to identify and extract the active ingredients and corresponding targets of the Fuyanjie formula. The collective targets were then intersected with the disease targets "pruritus", "dermatitis", and "skin allergy", which were obtained from the GeneCards database, in order to identify the core targets. The String database, Cytoscape software, and the cytoHubba plug-in were utilized to construct and analyze the protein-protein interaction (PPI) network, and the key hub genes were subsequently identified and quantified. A GO function analysis and KEGG enrichment analysis of core action targets were conducted utilizing the DAVID database.[Results] A total of 87 active ingredients were identified from the Fuyanjie formula through a screening process, which corresponded to a total of 254 targets of action. Through intersection analysis, 41 core targets of the Fuyanjie Chinese herbal formula were identified, which contribute to its anti-inflammatory, anti-pruritic, and anti-allergic effects. The findings indicated that quercetin, beta-sitosterol, stigmasterol, formononetin, luteolin, and other bioactive compounds present in the Fuyanjie Chinese herbal formula may interact with the targets IL-6, MMP-9, TNF, and IL-1β. These compounds were suggested to exert anti-inflammatory, anti-pruritic, and anti-allergic effects through pathways associated with the inflammatory response, including the IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway, etc.[Conclusions] Fuyanjie Chinese herbal formula may modulate skin conditions through a multifaceted mechanism of action that involves multiple components, targets, and pathways.

Effect of Boschniakia rossica on expression of GSTP,p53 and p21^(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats

AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21rasproteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21rasproteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H2O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21rasproteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH2Cl2 and H2O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H2O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH2CI2 and H2O extracts from BR exerted anti-inflammatory effect in rats and mice.

Phytopharmacological potential of different species of Morus alba and their bioactive phytochemicals:A review

Medicinal plants of Moraceae family have been well-recognized traditionally due to their versatile applications in various fields including agriculture, cosmetic and food as well as in pharmaceutical industries. Their biomedical and medicinal importance is reflected from their broad range of pharmacological activities for treatment of various inflammatory conditions, cancer, infectious diseases, and gastrointestinal disorders. The present review was aimed to summarize and critically discuss the biomedical implications of Morus species, their bioactive compounds, and phytochemicals. Bioactivity guided fractionation of these medicinal plants revealed that different types of bioactive phytochemicals and secondary metabolites such as steroids, saponins, alkaloids, glycosides and phenolic compounds including terpenoids, flavonoids, anthocyanins and tannins were present. The critical analysis of the literature revealed that the aqueous, methanolic, and ethanolic extracts of Morus species and their bioactive compounds exhibit remarkable anti-oxidative,anti-diabetic, anti-stress, nephroprotective, antimicrobial, anti-mutagenic, anticancer,anxiolytic, hepatoprotective, anthelmintic, antimicrobial, immune-modulatory and cholesterol lowering effects. Based on the literature review and bioactivity guided investigation of Morus species and their phytomedicinal effects, we anticipate that these herbal products hold excellent potential for future research.

Protective effects of pharmacological therapies in animal models of multiple sclerosis: a review of studies 2014–2019

Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.

Plant distribution and pharmacological activity of flavonoids

Flavonoids are natural organic compounds that are widely found in nature, their structural types are complex, and they mainly include flavonoids, flavonols, dihydroflavonols, isoflavones, dihydroisoflavones, chalcones, orange ketones, flavanoids, anthocyanidins, and biflavonoids. This review covers the plant distribution and pharmacological activities of flavonoids. Flavonoids are mainly distributed in angiosperms and gymnosperms, and they are abundant in plants such as Rutaceae, Labiatae, Zingiberaceae, Scrophulariaceae, and Leguminosae. Because of their wide distribution and variety, researchers have found that flavonoids have diverse biological activities, mainly focusing on anti-inflammatory, antibacterial and antitumor activities. Mechanistically, the anti-inflammatory effects are mainly related to the NF-κB and MAPK (mitogen-activated protein kinase) signaling pathway and then the inhibition of the production of inflammatory cytokines and mediators. The antibacterial activity is mainly manifested as inhibitory effects on many strains, including Escherichia coli, Cryptococcus neoformans, and Pseudomonas aeruginosa, via destroying the stability of the microbial membrane, inhibiting the invasion of virulent bacteria into host cells, promoting the apoptosis of bacteria, inhibiting bacterial fatty acid synthesis, etc. The antitumor activity of flavonoids is related to their inhibition of cell proliferation and induction of apoptosis via the mitochondria-mediated, endoplasmic reticulum-mediated, and death factor and its receptor-mediated signal transduction pathways. Understanding the plant distribution and pharmacological activity of flavonoids not only reveals the importance of identifying such valuable flavonoids in another genus or family but also provides a basis for fully exploiting the therapeutic potential of flavonoids.

Directional migration of leukocytes: their pathological roles in inflammation and strategies for development of anti-inflammatory therapies

Directional migration of leukocytes is indispensable to innate immunity for host defense. However, recruitment of leukocytes to a site of tissue injury also constitutes a leading cause for inflammatory responses. Mechanistically, it involves a cascade of cellular events precisely regulated by temporal and spatial presentation of a repertoire of molecules in the migrating leukocytes and their surroundings (microenvironments). Here I will summarize the emerging evidence that has shed lights on the underlying molecular mechanism for directional migration of leukocytes, which has guided the therapeutical development for innovative anti-inflammatory medicines.

Study on Pharmacological Effects of Calycosin in Astragali Radix

Calycosin is an important isoflavone compound in traditional Chinese medicine Astragali Radix.It not only has remarkable anti-oxidation,anti-inflammatory and anti-tumor functions,but also has the characteristics of small adverse reactions and low toxicity,so it has attracted wide attention of scholars and researchers.This paper reviewed the pharmacological effects and mechanisms of calycosin in recent years,in the hope of providing a theoretical basis for its clinical application.

Effective anti-inflammatory phenolic compounds from dandelion:identification and mechanistic insights using UHPLC-ESI-MS/MS,fluorescence quenching and anisotropy,molecular docking and dynamics simulation

This novel study identifi es the effective anti-inflammatory phenolic compounds in dandelion and provides mechanistic insights into their interactions with receptor proteins(toll-like receptor 4,TLR4;co-receptor myeloid differentiation protein-2,MD-2)using UHPLC-ESI-MS/MS,lipopolysaccharide(LPS)-stimulated THP-1 cell line,fluorescence quenching and anisotropy,molecular docking(single ligand and multi-ligand docking)and molecular dynamics simulation.A 50%aqueous methanol extract had a greater anti-inflammatory effect and higher chicoric acid content,compared with the 100%water and 100%methanol extracts.Chicoric acid,chlorogenic acid,methylophiopogonone A,caffeic acid,gallic acid monohydrate and 4’-O-demethylbroussonin A had relatively high binding energies and contents in all extracts.Chicoric acid competed with chlorogenic acid,4’-O-demethylbroussonin A and quercetin for MD-2.Among dandelion’s phenolics,chicoric acid most effectively hindered TLR4-MD-2 complex formation,with a quenching constant of 0.62×10^(6) L/mol for MD-2 or TLR4 at 320 K,and binding energies of-6.87 and-5.97 kcal/mol,respectively,for MD-2 and TLR4.

Pharmacological strategies for Parkinson’s disease

Parkinson’s disease (PD) or Paralysis Agitans was first formally described in “An essay on the shaking palsy”, published in 1817 by a British physician named James Parkinson. In the late 1950’s, dopamine was related with the function of the corpus striatum, thus with the control of motor function. But it was not until 1967, when the landmark study of George C. Cotzias, demonstrated that oral L-DOPA, the precursor of dopamine metabolism, was shown to induce remission of PD symptoms, that the definitive association between the two was firmly established. However, later on L-DOPA treatment began to show a loss of effectiveness and demonstrated to induce a variety of undesirable effects, the most prominent being diskinesia. As a result of this, a variety of alternative or complementary pharmacological strategies have been developed. In this chapter we review the wide variety of strategies that have been used through time, which are geared toward reducing the most disabling symptoms of PD. We additionally make some suggestions as to which are the most promising ones.

Network pharmacological study on the annti-inflammatory mechanism of XuanBaiChengQi Decoction in the treatment of novel coronavirus pneumonia (COVID-19)

Objective:To clarify potential molecular mechanism of annti-inflammatory and signal pathways of XuanBaiChengQi(XBCQ)Decoction in treatment on COVID-19.Methods:The active ingredients and targets of XBCQ Decoction were searched from the TCMSP、literature and Swiss Target Prediction.COVID-19 pneumonia targets were obtained by the GeneCards.A protein-protein interaction(PPI)network was constructed through the STRING database.Metascape datebase was used to perform Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.And then Cytoscape 3.7.2 software was used to create an active ingredients-target-disease network.Results:Apart from gypsum,XBCQ Decoction contains 3 herbs,52 compounds and 674 relavent targets.The targets of the main active ingredients of XBCQ Decoction were intersected with the therapeutic targets of the COVID-19 pneumonia,obtaining 78 key targets.Network of drug components-target-disease indicated that 5 compounds(e.g.α-Spinasterol、Chrysophanic acid、Palmidin A、Vitamin-e、Physcion)play crusial role in treatment.Conclusion:From these ways,we found some key molecular targets,such as CYP19A1,PTGS2,EGFR,BCL2,HMGCR,PPARG,NOS2,SLC6A4,MAPK1,MAPK3.These targets jointly participate in the regulation of Pathways in cancer,MAPK signal pathway,Jak-STAT signal pathway and many other signal pathways,among which anti-inflammatory effect may be the main mechanism of XuanBaiChengqi Decoction.

Anti-inflammatory,Bacteriostatic and Anticancer Effects of Madecassoside

Madecassoside is a natural active component extracted from Centella asiatica.In recent years,a large number of studies have reported that madecassoside has a variety of biological activities,such as anticancer,anti-inflammatory and antibacterial effects,prevention and treatment of cardiovascular diseases,nerve damage,visceral damage and arthritis,and other pharmacological effects.In this paper,the pharmacological action and mechanism of madecassoside were reviewed to provide a theoretical basis for further research of madecassoside and drug development.

Some pharmacological studies on the methanolic extract of <i>Inula graveolense</i>L.

Inula graveolens L. is widely used in Iraq for the treatment of rheumatic fever, infant convulsions, toothache, blood sugar, and also to dissolve internal blood clots, and to aid digestion. However, the efficacy and mechanisms of action of the plant remain unclear. Therefore, the objective of the present study was to investigate the pharmacological effects of the methanolic extract (MEIG) of this plant belonging to compositae family. Anti-diarrheal and antipyretic activities of the extract were examined in rats. Anti-inflammatory and antinociceptive were studied in mice. At the doses of 200 (P in vitro protein anti-denaturation using Bovine serum albumin and anti-platelet aggregation of human blood activity. It was observed that the extract showed greater percentage of inhibition of BSA (P potential platelet aggregation inhibitory activity in adose-dependent manner. The maximum inhibition was observed at the dose 400 μg/ml

A Non-Invasive Skin Treatment Combining LED with Pharmacologic and Ultrasonic Technologies for Facial Rejuvenation

Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .

四逆散药理作用及治疗内科疾病的临床应用研究

四逆散为《伤寒论》中记载的经典名方,至今约有1800年的历史,适用于少阴病症,临床多以手足不温、泄利下重、腹痛、脉弦等为辨证要点,具有透邪解郁、疏肝理脾之功效。中医认为该方剂治疗病症与阳衰阴盛有本质的区别,该证属外邪传经入里,气机为之郁遏,失于疏泄,阳气内郁不能达于四末所致,为阴中涵阳、惟气不宣通而致四肢逆冷。四逆散的应用十分广泛,几乎各系统疾病均可以该方剂为基础方进行辨证施治,尤其是现临床对四逆散的研究更加深入,其药理作用和应用领域也进一步被拓展,可广泛用于治疗胃肠肝胆疾病、精神类疾病、肿瘤疾病等。文章通过分析近年来四逆散的应用文献,总结其药理和治疗作用,为临床对四逆散有更加深入地了解,推动该方剂在临床的进一步开发应用。

Notch信号通路——对健康和疾病的机械论观点

The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Serrate/Jagged)where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains,relative to their intracellular portions.Upon interaction of the core binding regions,presented on opposing cell surfaces,formation of the receptor/ligand complex initiates force-mediated proteolysis,ultimately releasing the transcriptionally-active Notch intracellular domain.This review focuses on structural features of the extracellular receptor/ligand complex,the role of posttranslational modifications in tuning this complex,the contribution of the cell membrane to ligand function,and insights from acquired and genetic diseases.

Effects of herbal extracts and compounds and pharmacological agents on pulmonary fibrosis in animal models:a review

Pulmonary fibrosis, a chronic inflammatory disease that occurs mainly in older adults, is a serious health threat with few effective treatment options. The etiological aspects of pulmonary fibrosis remain unknown, though some factors such as cigarette smoking, viral infections, surfactant protein polymorphisms, and chronic or high doses use of certain drugs are considered to be risk factors for the progression of pulmonary fibrosis. No standard treatments have been introduced in clinic yet. Although glucocorticoids and antioxidant drugs have been administered, the severe and broad-spectrum adverse effects of glucocorticoids limit their use. Efforts to identify novel therapeutic agents with improved safety profiles are therefore ongoing. In this review, the authors have described the effects of herbal extracts and compounds and certain pharmacological agents on pulmonary fibrosis in animal models. These effects indicate that herbs are a promising source of compounds that can play pivotal roles in the treatment of lung fibrosis.