Pharmacological intervention for chronic phase of spinal cord injury

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

Pharmacological Studies of Meisoindigo: Absorption and Mechanism of Action

Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoindigo, compared to indirubin to be one of the major reasons for the enhancement of antitumor activity. Studies on the mechanism of meisoindigo action indicate that it strongly inhibits DNA biosynthesis in tumor cells. Strong inhibition of the drug on assembly of microtubule protein was also obtained. By means of FCM technique the effects of meisoindigo on mouse leukemia L1210 cell cycle were examined. Experimental results showed that under the action of meisoindigo the S phase cells accumulated and the traverse of the cells in G2 + M phase to G1 phase may also be blocked to some extent.

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.

Clinical pharmacological studies in children: From exploratory towards confirmation driven methodology

Just like children are not small adults, pediatric studies are not just subgroup-adult studies. Clinical pharmacology aims to predict these effects based on drug, population and/or patient-specific pharmacokinetics(concentration-time profiles) and-dynamics(concentration-effect profile). The most essential characteristics of childhood are growth and maturation. Both phenomena are most prominent during infancy making the claim that "an infant is not just a small child" as relevant compared to the paradigm that "a child is not just a small adult". From a clinical pharmacology perspective, the consequence of such a dynamic setting is extensive variability throughout childhood in both the pharmacokinetics and pharmacodynamics. Trial design probably has impact on recruitment to an even greater extent compared to adult studies. In general, if a study is designed well, with a clear clinical question with which parents and children can identify, they are likely to consider participation. Open communication with all stakeholders involved will most likely result in ethically correct, practically feasible, scientifically sound, and economical reasonable studies to provide children with the appropriate treatment. From an academic perspective, feasibility, relevance, applicability and costs of clinical pharmacological studies in children can be signifi cantly improved by new sampling concepts(e.g., saliva, urine, dried spot blood) and the systematic introduction of already known information into the trial design through model based pediatric drug development, that mainly affect feasibility of pharmacokinetic studies. In contrast, for the pharmacodynamic part of pediatric studies, development and validation of population specifi c biomarkers or robust outcome variables is urgently needed.

The Pharmacological and Toxicological Studies of Tou Tong Shen Xiao Dan

Tou Tong Shen Xiao Dan(TTSXD)consisted of traditional Chinese Medicines including:Chuanxion(Ligustici Chuanxiong),Hounghua(Salt lower),Taoren(Peach seed),Gouteng(Hooked Uncaria),Xixin(Herb Asari)and Baizhi(Dahurian angelica root)etc.The results of thepresent study showed that TTSXD had strong sedative and analgesic effects and could dilate thblood ves-sels,lower blood presure,increase cerebral blood flow(CBF),raise the ability to tolerate hypoxia.Improve the microcirculation,prevent platelet aggregation and reduce the visicosity of the wholeblood. Acute and subacute toxicological studies didn’t demonstrate toxic and side effects on livingbodies.

Phytochemicals,pharmacological and ethnomedicinal studies of Artocarpus:A scoping review

This article aims to review the scientific data on phytochemical and pharmacological studies of Artocarpus collected from Malaysia as well as to highlight their usage as ethnomedicine worldwide.About 55 Artocarpus species are distributed worldwide and 32 of the Artocarpus species can be found in Malaysia.Artocarpus species are well known worldwide for their edible fruits such as Artocarpus heterophyllus(jackfruit),Artocarpus integer(chempedak),and Artocarpus communis(breadfruit).Aside from its edible fruits,the timber is valued for light constructions,crates,large canoes,and boats.The literature for this review was searched using the term‘Artocarpus’,‘Artocarpus Malaysia’,‘Artocarpus extracts’,‘Artocarpus traditional medicine’and‘Artocarpus ethnomedicine’from published books and scientific journals via various engines such as The Web of Science,PubMed,Science Direct,Scopus,Research Gate,and Google Scholar.The references cited from the retrieved articles were also scanned and cross-checked.All published studies on phytochemical and pharmacological activities of Malaysia’s Artocarpus species up to January 2021 were included in this review.Articles on phytochemical studies of Malaysia’s Artocarpus revealed the isolation of flavonoids as the major constituents.Research on pharmacological activities of the isolated phytochemicals showed that these compounds exhibited significant disease-linkedenzyme(tyrosinase,cholinesterase,glucosidase)inhibitors as well as antioxidant,anti-inflammatory,antimicrobial,and cytotoxic activities.The ethnomedicinal data gathered are useful to understand and prioritize Artocarpus species that can contribute to potent phytochemicals and possibly new drug leads.This review also provides valuable information for the future development of isolated compounds from Artocarpus species.

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

Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Advances in Pharmacological Studies of Calycosin-7-O-β-D-glucoside

The isoflavone compound Calycosin-7-O-β-D-glucoside (CG) is an active monomer component extracted from the dry roots of the leguminous plant Astragalus mongolicus and Astragalus. It is also one of the main active ingredients in the Astragalus that is a commonly used traditional herb. CG has obvious effects of anti-oxidation, anti-virus, inhibition of melanin formation, and immunosuppression. With the advancement of modern technology, it has become a pivotal subject that the adjuvant therapy or even substitute for the synthetic drug of monomer of Chinese herb in medical field. In recent years, with the deepening of research on the mechanism of action of CG, which has been found that its pharmacological effects are very extensive, such as the anti-tumor effect and the effect on cerebrovascular diseases of CG. This review summarizes the pharmacological effects and the latest research progress of CG.

Pharmacological, Microbiological and Derivatographic Studies of the Solid-Dosage Form of the Immunomodulatory Drug Made on the Basis of Bee Products

Pharmacological, derivate and microbiological study of beebread based immunomodulatory drug was conducted. Iimmunomodulating properties of pellets ＂Apimun＂ in the form of antibodies formation in response to the EB antigen were studied. Clear immunostimulatory properties of pellets ＂Apimun＂ were reproduced in mature rats and mice with normal immune status. Pellets ＂Apimun＂ at doses 1.5 and 2.0 g/kg showed increased activity ofphagocytosis and processes of antibody formation inhibition of delayed hypersensitivity reactions. Antimicrobial activity of pellets ＂Apimun＂ was studied. It was proved that it did not have antimicrobial properties. Derivate studies were conducted and showed that the active substance and composition of the IMP was stable at normal temperature. The results of pharmacological, microbiological and derivate studies show the effectiveness of the pellets ＂Apimun＂ and prospects for further research in order to create a product for immune status improvement.

Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

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.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Pharmacological Treatment for Atrial Fibrillation—Modalities in Equines and Companion Animals

Cardiac arrhythmias are probably more common in horses than in any other domestic animal species where poor performance and exercise intolerance is the most frequent clinical complaint. Atrial fibrillation is a type of cardiac arrhythmia that appears as a common finding during medical examinations in humans, large breed dogs and horses. Clinical presentations are of a particular value in racehorses in high performing activities. Atrial fibrillation is characterized by an irregular heart rhythm, secondary to a primary disease or without any sign of comorbidity. The generation and maintenance of Atrial Fibrillation requires a substrate. Some breeds have a genetic predisposition to developing Atrial Fibrillation. Most cases of Atrial Fibrillation are of the paroxysmal type and self-regulate within a few hours to days without the need for treatment. The focus of this study is on the arrhythmic agents that are used for the treatment of Atrial Fibrillation, therefore other arrhythmic agents may not be included, or are included to demonstrate their effect on increasing, inhibiting or decreasing efficacy when used together with medications for the treatment of Atrial Fibrillation. The “working horse” for the pharmacological treatment of Atrial Fibrillation is Quinidine.

Phytochemical Studies, Antimicrobial and Anti-Inflammatory Properties of the Hydroethanolic Extract of Kalanchoe pinnata (Lam.) Pers. from Togolese Flora

Kalanchoe pinnata (Lam.) Pers. is known as a plant that has many special benefits such as anti-inflammatory and antibacterial. The present study was carried out to perform a phytochemicals study and evaluate the antimicrobial and anti-inflammatory activity of the hydroethanolic extract of Kalanchoe pinnata (Lam.) Pers. leaves. After phytochemicals screening, the content of phenolic compounds, proanthocyanidol and flavonoids in the extract of this plant was determined spectrophotometrically. Antimicrobial activity was assessed using the micro-dilution technique on 96-well plates in liquid medium, combined with agar spreading. Anti-inflammatory activity was assessed using the 1% carrageenan induced rat paw oedema model. Phytochemical screening revealed the presence of alkaloids, saponins, triterpenes and sterols, phenols and flavonoids in the plant extract in varying proportions. The extract contained (0.049 ± 0.03 µg EAG/mg extract) total polyphenols, (0.215 ± 0.025 µg CE/mg extract) proanthocyanidins and (385.435 ± 0.0328 µg ER/mg ES) flavonoids. The hydroethanolic extract of the leaves of this plant inhibited the in vitro growth of the microbial strains studied to varying degrees. The MIC of the extract varied from 12.5 to 25 mg/mL and the BMC from 12.5 to 50 mg/mL. The plant did not show any activity on 1% carrageenan-induced rat paw edema.

Pharmacological effects of volatile oil from chrysanthemum and its associated mechanisms:a review

Volatile oil(VO)is the main chemical component of common plants in Chrysanthemum genus,and it possesses several beneficial pharmacological properties,including bacteriostatic,antioxidant,anti-tumor,anti-inflammatory,antipyretic,analgesic,antiosteoporotic,antihypertensive,sedative,and hypnotic effects.To date,research on the effective components of Chrysanthemum extract has mainly focused on flavonoids,whereas limited data are available on the chemical constituents and underlying mechanisms of action of the VO components.In this review,the pharmacological activities and mechanisms of VO are comprehensively reviewed with the aim of providing a foundation for further development for medicinal,aromatherapy,and diet therapy applications.

Boswellic acids: a review on its pharmacological properties, molecular mechanism and bioavailability

Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Qizhu prescription for treating breast cancer

Objective:To investigate the mechanism underlying the effects exerted by the Qizhu prescription(QZP)in breast cancer(BC),and the respective targets.Methods: Expression data from the ArrayExpress and The Cancer Genome Atlas(TCGA)were used to identify differentially expressed genes(DEGs)in BC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions.Molecular docking was used to explore the dynamic relationship between active molecules and targets.Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior.Results: Among the 25 evaluated BC-related targets of QZP,matrix metalloproteinase-1(MMP1)and epidermal growth factor receptor(EGFR)exhibited the highest degrees of dysregulation.GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells.Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin,as well as between MMP1 and luteolin/kaempferol/quercetin.Quercetin significantly reduced BC cell proliferation,migration,invasion,and tumor development in vivo.Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins.Conclusion: The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC,with particular reference to QZP.

Research Progress on Purification Process, Content Determination and Pharmacological Action of Atractylodin

Atractylodis Rhizoma comes from the dry rhizome of Atractylis lancea or Atractylodes chinensis in the Compositae family,and it is suitable for preventing and treating diseases such as cold,edema,night blindness and rheumatic arthralgia.Atractylodin is the main active component extracted and isolated from Atractylodis Rhizoma.A large number of studies have found that atractylodin has excellent drug activity in improving gastrointestinal emptying,anti-inflammation,inhibiting malignant tumor and reducing blood lipid.In this paper,the purification process and pharmacological activity of Atractylodin were summarized to provide a theoretical basis for basic research,clinical application and further development and utilization of atractylodin.

Gentiana macrophylla Pall.:a review of the basic source,traditional use,chemical components,pharmacological activities and quality control

Gentiana macrophylla Pall.(G.macrophylla),whose genus and family belong to the Gentianaceae and Gentiana.The main distribution centers of G.macrophylla resources were the Loess Plateau and the eastern Qinghai-Tibet Plateau in China.G.macrophylla,as a traditional medicine,has a long history and was used in different ethnic medicines.Its roots were used in traditional Chinese medicine,which had the effect of anti-inflammatory,anti-rheumatism,antiviral,promote blood circulation,eliminate swelling and pain,while its flowers were used in traditional Mongolian medicine,which had the effect of removing“Xieriwusu”(“Xieriwusu”means rheumatism),antiviral,reducing swelling.From previous studies,it could be found that there were more than forty components isolated and identified from G.macrophylla.The main chemical components were iridoids,flavonoids,triterpenoids,steroids,phenylpropanoids,and alkaloids.Iridoid terpenoid components represented by gentiopicroside and Loganic acid were the main components of the root of G.macrophylla,which had anti-inflammatory,antioxidant,hepatoprotective,analgesic,antibacterial and promote gastrointestinal tract activities.The flower mainly contains isoorientin and isovitexin as the representative of flavonoids.They have anti-tumor,liver protection,heart protection,inhibition of acetylcholinesterase and inhibition of melanin.It could be seen from previous studies that the research on G.macrophylla was mainly focused on the root,and the flower was rarely studied.It was reported that the experimental data of the anti-inflammatory and anti-tumor effects of G.macrophylla flowers show that its curative effect was very good.Therefore,the flowers of the flower of G.macrophylla can be used as potential medicinal parts for research.Given that flavonoids are mostly found in flowers and exhibit a range of functions,it is possible to investigate the flowers in order to learn more about G.macrophylla’s potential medical benefits.Based on botanical books,Chinese classic texts,medical monographs and academic search engines(Google,Google Scholar,Web of Science,SciFinder,Pubmed,CNKI,Sci-hub,Elsevier and Wanfang),the data and information on G.macrophylla in the past 20 years are inquired and summarized comprehensively.The basic source,traditional use,chemical composition,biological activity,pharmacodynamics and quality control of G.macrophylla was systematically reviewed,in order to provide reliable basis for the subsequent development and utilization of G.macrophylla.