Health functions and related molecular mechanisms of Miconia genus: A systematic review.

The Miconia genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted genus of medicinal plants widely used to treat rheumatoid arthritis (RA), pain, inflammatory diseases, and many more therapeutic applications. In the present study, we systematically identify and discuss the literature on in vivo and in vitro studies focusing on the therapeutic potentials and related molecular mechanisms of the Miconia genus. The review also assessed phytochemicals and their pharmacological properties and considered safety concerns related to the genus. Literature searches to identify studies on the Miconia genus were carried out through four main electronic databases, namely PubMed, Embase, Scopus, and Web of Science limited to Medical Subjects Headings (MeSH) and Descriptores en Ciencias de la Salud (DCS) (Health Sciences Descriptors) to identify studies published up to December 2022. The relevant information about the genus was gathered using the keywords 'Miconia', 'biological activities', 'therapeutic mechanisms', 'animal model, 'cell-line model', 'antinociceptive', 'hyperalgesia', 'anti-inflammatory', and 'inflammation'. The therapeutic potentials and mechanisms of action of 14 species from genus Miconia were examined in 18 in vitro studies and included their anti-inflammatory, anticancer, analgesic, antibacterial, cytotoxic, mutagenic, antioxidant, anti-leishmanial, antinociceptive, schistosomicidal, and anti-osteoarthritis potentials, and in eight in vivo studies, assessing their analgesic, antioxidant, antinociceptive, and anti-osteoarthritis activities. Some of the main related molecular mechanisms identified are the modulation of cytokines such as IL-1ß, IL-6, and TNF-α, as well as the inhibition of inflammatory mediators and prostaglandin synthesis. The limited number of studies showed that commonly available species from the genus Miconia are safe for consumption. Miconia albicans Sw.Triana and Miconia rubiginosa (Bonpl.) DC was the most frequently used species and showed significant efficacy and potential for developing safe drugs to treat pain and inflammation.

Anti-inflammatory and modulatory effects of steroidal saponins and sapogenins on cytokines: A review of pre-clinical research.

BACKGROUND: Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models. PURPOSE: The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines. STUDY DESIGN AND METHODS: This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved. RESULTS: Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways. CONCLUSION: Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation.

Biological properties of terpinolene evidenced by in silico, in vitro and in vivo studies: A systematic review.

BACKGROUND: Terpinolene, a monoterpene that is naturally found in a variety of herbs, is widely used as a flavoring agent in the industry. Although it's well established in the literature that terpinolene is an important component of plant extracts, the biological properties and the potential therapeutic use of this compound remain poorly explored. PURPOSE: This work aimed to answer the following guiding question: "What are the biological activities of terpinolene demonstrated through in silico, in vitro, and in vivo assays?". STUDY DESIGN AND METHODOLOGY: A systematic review was carried out in four electronic databases (Embase, Web of Science, Scopus, and PubMed) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using the following search terms: terpinolene "AND" activity "OR" properties "OR" therapeutic "OR" treatment. This search included manuscripts published between 1960 and June 2020. Study selection was conducted by two independent reviewers according to predefined criteria. RESULTS: The initial search found a total of 2449 articles. However, only 57 of them were selected as they met the inclusion criteria and answered the guiding question. The analysis of these studies indicated that terpinolene presents a series of biological effects, from which the antioxidant, larvicide, and insecticide activities stand out. Despite the evidence demonstrating that terpinolene has the potential to be used in a broad pharmacological context, the mechanisms underlying its cellular and molecular effects remain to be better elucidated. In addition, the in vivo efficacy and safety of the administration of this compound have been poorly evaluated through either preclinical and clinical trials. Therefore, this study highlights the importance of characterizing the biological aspects and mechanisms of action of this natural compound. CONCLUSION: The data summarized in the present systematic review demonstrates the pharmacological potential of terpinolene. Nevertheless, most studies included in this review provide a superficial characterization of terpinolene biological effects and therefore, further research elucidating its mechanism of action and potential therapeutic benefits through preclinical and clinical trials are required. Nevertheless, due to its wide range of different biological activities, terpinolene will certainly attract the interest of scientific research, which could significantly contribute to the development of new products with both therapeutic and environmental applications.

Modulation of interleukin expression by medicinal plants and their secondary metabolites: A systematic review on anti-asthmatic and immunopharmacological mechanisms.

BACKGROUND: Asthma is one of the most common chronic inflammatory conditions of the lungs in modern society. Asthma is associated with airway hyperresponsiveness and remodeling of the airways, with typical symptoms of cough, wheezing, shortness of breath and chest tightness. Interleukins (IL) play an integral role in its inflammatory pathogenesis. Medicinal herbs and secondary metabolites are gaining considerable attention due to their potential therapeutic role and pharmacological mechanisms as adjunct tools to synthetic bronchodilator drugs. PURPOSE: To systematically review the literature on the use of single or mixed plants extracts therapy in vivo experimental systems for asthma, emphasizing their regulations on IL production to improve lung. METHODS: Literature searches were performed on PubMed, EMBASE, Scopus and Web of Science databases. All articles in English were extracted from 1999 up to September 2019, assessed critically for data extraction. Studies investigating the effectiveness and safety of plant extracts administered; inflammatory cell count, immunoglobulin E (IgE) production and regulation of pro-inflammatory cytokine and T helper (Th) 1 and Th2-driven cytokine expression in bronchoalveolar lavage fluid (BALF) and lung of asthmatic animals were included. RESULTS: Four hundred and eighteen publications were identified and 51 met the inclusion criteria. Twenty-six studies described bioactive compounds from plant extracts. The most frequent immunopharmacological mechanisms described included reduction in IgE and eosinophilic recruitment, decreased mucus hypersecretion and airway hyperreactivity, enhancement of the balance of Th1/Th2 cytokine ratio, suppression of matrix metallopeptidase 9 (MMP-9) and reversal of structural alterations. CONCLUSION: Plant extract therapies have potential control activities on asthma symptoms by modulating the secretion of pro-inflammatory (IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10, IL-23, IL-31, IL-33), Th1 (IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines, reducing the level of biomarkers of airway inflammation.

Antinociceptive and anti-inflammatory effect of Poincianella pyramidalis (Tul.) L.P. Queiroz.

ETHNOPHARMACOLOGY RELEVANCE: Poncianella pyramidalis (Leguminosae) is a Caatinga plant used in folk medicine because of its pharmacological properties, which include anti-inflammatory action. However, chemical compounds responsible for this effect have not yet been identified. AIM OF THE STUDY: This study aimed to evaluate the antioxidant, antinociceptive and anti-inflammatory effects of the ethyl acetate fraction from the inner bark of P. pyramidalis. MATERIAL AND METHODS: Total phenol content (TP) was estimated using the Folin-Ciocalteu reagent, while in vitro antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Chemical identification was done using LC-PDA/MS and LC-ESI/MS/MS. In vivo antinociceptive and anti-inflammatory properties were investigated using formalin, mechanical hypernociception and carrageenan-induced pleurisy assays in mice. RESULTS: TP was 525.08 ± 17.49 µg mg-1 gallic acid equivalent. The ethyl acetate fraction (EAF) inhibited 87.76% of the DPPH radical with an EC50 of 22.94 µg mL-1 and Antioxidant Activity Index of 1.74. LC-PDA/MS and LC-ESI/MS/MS identified 15 compounds that are mostly derived from gallic and ellagic acids. Regarding in vivo antinociceptive and anti-inflammatory activity, EAF (100 mg kg-1) significantly reduced the nociceptive response in the second phase of the formalin assay by 50% (p < 0.01) compared with the control group. In the hypernociception test, a significant (p < 0.001) anti-hyperalgesic effect of EAF (100 mg kg-1) was observed up to the third hour of evaluation (p < 0.001). In the carrageenan assay, EAF (100 mg kg-1) was shown to inhibit protein extravasation, increase total leukocytes and neutrophils, and inhibit mononuclear cells. CONCLUSION: These results demonstrate EAF from the inner bark of P. pyramidalis has strong in vitro antioxidant effect as well as in vivo antinociceptive and anti-inflammatory activities, which may be attributed to the bark being rich in phenolic compounds derived from gallic acid.

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties.

BACKGROUND: Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities. PURPOSE: We reviewed whether essential oils and their bioactive compounds of plant origin could modulate cytokines' immune responses and improve asthma therapy in experimental systems in vitro and in vivo. METHODS: Electronic and manual search of articles in English available from inception up to November 2018 reporting the immunomodulatory activity of essential oils and their bioactive compounds for the management of asthma. We used PubMed, EMBASE, Scopus and Web of Science. Publications reporting preclinical experiments where cytokines were examined to evaluate the consequence of anti-asthmatic therapy were included. RESULTS: 914 publications were identified and 13 were included in the systematic review. Four articles described the role of essential oils and their bioactive compounds on bronchial asthma using cell lines; nine in vivo studies evaluated the anti-inflammatory efficacy and immunomodulating effects of essential oil and their secondary metabolites on cytokines production and inflammatory responses. The most important immunopharmacological mechanisms reported were the regulation of cytokine production, inhibition of reactive oxygen species accumulation, inactivation of eosinophil migration and remodeling of the airways and lung tissue, modulation of FOXP3 gene expression, regulation of inflammatory cells in the airways and decreasing inflammatory mediator expression levels. CONCLUSION: Plant derived essential oils and related active compounds have potential therapeutic activity for the treatment of asthma by modulating the release of pro-inflammatory (TNF-α, IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10), Th1 (IFN-γ, IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines and the suppression of inflammatory cell accumulation.

Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models.

BACKGROUND: Flavonoids are naturally occurring compounds, extensively distributed in plants. T helper (Th)1 and Th2 cytokines balance plays an essential role in the reaction of inflammatory, allergic and infectious processes and transplantation rejection. PURPOSE: This systematic review focuses on various classes of flavonoids with a view to evaluate whether Th1/Th2 cytokine-mediated pathways of immunoenhancement could reduce immune overwhelming reactions. METHODS: Articles in English published from inception to December 2017 reporting flavonoids with immunomodulatory activity for the management of immune-mediated disorders were acquired from PubMed, EMBASE, Scopus and Web of Science and a animal experiments where Th1 and Th2 cytokines were investigated to assess the outcome of immunoregulatory therapy were included. CHAPTERS: 1809 publications were identified and 26 were included in this review. Ten articles described the effect of flavonoids on allergic inflammation in an animal model of asthma; eleven in vivo studies evaluated the immunomodulating and immunosuppressive effects of flavonoids on Th1/Th2 cytokines production and five reports described the regulatory role of flavonoids for Th1/Th2 cytokine responses to experimental arthritis and myocarditis. Modulation of Th1/Th2 cytokine balance, inhibition of eosinophil accumulation and remodeling of the airways and lungs, downregulation of Notch and PI3K signaling pathways, regulation of CD4 + /CD8 + lymphocytes ratio and decreasing inflammatory mediator expressions levels are among the most important immunopharmacological mechanisms for the retrieved flavonoids. CONCLUSION: Naturally occurring flavonoids discussed in the present article have optimal immunomodulation to prevent immune-mediated disorders through management of Th1/Th2 cytokine balance.

Antinociceptive effect of Aristolochia trilobata stem essential oil and 6-methyl-5-hepten-2yl acetate, its main compound, in rodents.

Aristolochia trilobata L. is an aromatic plant, popularly known as "mil-homens", and its essential oil (EO) is generally used to treat colic, diarrhea and dysentery disorders. We evaluated the antinociceptive effect of A. trilobata stem EO and of its major compound, the (R)-(-)-6-methyl-5-hepten-2-yl acetate (sulcatyl acetate: SA), using acetic acid (0.85%)-induced writhing response and formalin-induced (20 µL of 1%) nociceptive behavior in mice. We also evaluated the EO and SA effect on motor coordination, using the rota-rod apparatus. EO (25, 50 and 100 mg/kg) or SA (25 and 50 mg/kg) reduced nociceptive behavior in the writhing test (p<0.001). EO (100 mg/kg) and SA (25 and 50 mg/kg) decreased the nociception on the first phase of the formalin test (p<0.05). On the second phase, EO (25: p<0.01; 50: p<0.05 and 100 mg/kg: p<0.001) and SA (25 and 50 mg/kg; p<0.001) reduced the nociceptive response induced by formalin. EO and SA were not able to cause changes in the motor coordination of animals. Together, our results suggest that EO has an analgesic profile and SA seems to be one of the active compounds in this effect.

Medicinal plants and natural molecules with in vitro and in vivo activity against rotavirus: A systematic review.

BACKGROUND: Rotaviruses can cause life-threatening health disorders, such as severe dehydrating gastroenteritis and diarrhea in children. Vaccination is the main preventive strategy to reduce rotavirus diarrhea and the severity of episodes, but vaccines are not fully effective and new episodes may occur, even in vaccinated children. The WHO recommends oral rehydration therapy and zinc supplementation for rotavirus-induced diarrhea management. There is little preclinical evidence to support the use of phytotherapeutics in the management of rotaviral infections. PURPOSE: We aim to review the use of medicinal plants and natural molecules in the management of rotavirus infections in experimental studies. METHODS: Articles, published in the English language between 1991 and 2016, were retrieved from PubMed, Scopus and Web of Science using relevant keywords. The scientific literature mainly focusing on plant natural products with therapeutic efficacies against experimental models of rotavirus, were identified and tabulated. In addition, an assessment of the reliability of animal experiments was determined under ``Risk of Bias'' criteria. CHAPTERS: After an initial search and a revision of the inclusion criteria, 41 reports satisfied the objectives of the study. 36 articles were found concerning the anti-rotaviral potential in rotavirus infected cell lines. Among the active secondary metabolites screened for rotavirus inhibition, the polyphenols of flavonoid structure had acquired the highest number of studies in our survey, compared to phenolic acids, stilbenoids, tannins, pectins, terpenoids and flavonoid glycosides. Also, many phytochemicals reduced the efficacy of viral capsid proteins foremost to their elimination and improved the tendency of host-cell inhibiting virus absorption or by prevention of viral replication. Furthermore, five in vivo studies reported that herbs, as well its components, reduced the duration and severity of diarrhea in mice and piglets. The anti-rotavirus efficacy were highlighted based on improvements in reduction on liquid stool, fecal virus shedding, small intestinal histology, levels of inflammation related cytokines and signaling receptors. However, the quality of the experiments in animal studies contained certain types of bias in terms of how they were conducted and reported. CONCLUSION: We identified and summarized studies on medicinal plants and natural molecules having anti-rotavirus activity in order to further future developments of cures for rotavirus gastroenteritis.

A systematic review for anti-inflammatory property of clusiaceae family: a preclinical approach.

Background. Clusiaceae family (sensu lato) is extensively used in ethnomedicine for treating a number of disease conditions which include cancer, inflammation, and infection. The aim of this review is to report the pharmacological potential of plants of Clusiaceae family with the anti-inflammatory activity in animal experiments. Methods. A systematic review about experiments investigating anti-inflammatory activity of Clusiaceae family was carried out by searching bibliographic databases such as Medline, Scopus and Embase. In this update, the search terms were "anti-inflammatory agents," "Clusiaceae," and "animals, laboratory." Results. A total of 255 publications with plants this family were identified. From the initial 255 studies, a total of 21 studies were selected for the final analysis. Studies with genera Allanblackia, Clusia, Garcinia or Rheedia, and Hypericum showed significant anti-inflammatory activity. The findings include a decrease of total leukocytes, a number of neutrophils, total protein concentration, granuloma formation, and paw or ear edema formation. Other interesting findings included decreased of the MPO activity, and inflammatory mediators such as NF- κ B and iNOS expression, PGE2 and Il-1 ß levels and a decrease in chronic inflammation. Conclusion. The data reported suggests the anti-inflammatory effect potential of Clusiaceae family in animal experiments.

Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in ß-cyclodextrin.

Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/ß-cyclodextrin (ß-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26-30g) were pretreated with PC/ß-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/ß-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/ß-CD produced an antinocicepitve effect (p<0.01 or p<0.001) for 8h followed whereas isolated PC produced the same effect for 2h. Similar results were obtained in hot-plate test, PC/ß-CD, in all doses, significantly reduces (p<0.01 or p<0.001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose. Such results were unlikely to be caused by motor abnormality. Systemic pretreatment with PC/ß-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/ß-CD did so during a longer period when compared with isolated monoterpene alone. Our results provide evidence to propose that the complex with ß-CD improved analgesic and anti-inflammatory effects of p-cymene.

Effect of low-level laser therapy on pain levels in patients with temporomandibular disorders: a systematic review

Temporomandibular disorders (TMD) are characterized by the presence of temporomandibular joint (TMJ) and/or masticatory muscle pain and dysfunction. Low-level laser is presented as an adjuvant therapeutic modality for the treatment of TMD, especially when the presence of inflammatory pain is suspected. Objective: To systematically review studies that investigated the effect of low level laser therapy (LLLT) on the pain levels in individuals with TMD. Material and Methods: The databases Scopus, embase, ebsco and PubMed were reviewed from January/2003 to October/2010 with the following keywords: laser therapy, low-level laser therapy, temporomandibular joint disorders, temporomandibular joint dysfunction syndrome, temporomandibular joint, temporomandibular, facial pain and arthralgia, with the inclusion criteria for intervention studies in humans. exclusion criteria adopted were intervention studies in animals, studies that were not written in english, Spanish or Portuguese, theses, monographs, and abstracts presented in scientific events. Results: After a careful review, 14 studies fit the criteria for inclusion, of which, 12 used a placebo group. As for the protocol for laser application, the energy density used ranged from 0.9 to 105 J/cm², while the power density ranged from 9.8 to 500 mW. The number of sessions varied from 1 to 20 and the frequency of applications ranged from daily for 10 days to 1 time per week for 4 weeks. A reduction in pain levels was reported in 13 studies, with 9 of these occurring only in the experimental group, and 4 studies reporting pain relief for both the experimental group and for the placebo. Conclusion: Most papers showed that LLLT seemed to be effective in reducing pain from TMD. However, the heterogeneity of the standardization regarding the parameters of laser calls for caution in interpretation of these results. Thus, it is necessary to conduct further research in order to obtain a consensus regarding the best application protocol for pain relief in patients with TMD.

Effect of low-level laser therapy on pain levels in patients with temporomandibular disorders: a systematic review.

UNLABELLED: Temporomandibular disorders (TMD) are characterized by the presence of temporomandibular joint (TMJ) and/or masticatory muscle pain and dysfunction. Low-level laser is presented as an adjuvant therapeutic modality for the treatment of TMD, especially when the presence of inflammatory pain is suspected. OBJECTIVE: To systematically review studies that investigated the effect of low level laser therapy (LLLT) on the pain levels in individuals with TMD. MATERIAL AND METHODS: The databases Scopus, embase, ebsco and PubMed were reviewed from January/2003 to October/2010 with the following keywords: laser therapy, low-level laser therapy, temporomandibular joint disorders, temporomandibular joint dysfunction syndrome, temporomandibular joint, temporomandibular, facial pain and arthralgia, with the inclusion criteria for intervention studies in humans. exclusion criteria adopted were intervention studies in animals, studies that were not written in english, Spanish or Portuguese, theses, monographs, and abstracts presented in scientific events. RESULTS: After a careful review, 14 studies fit the criteria for inclusion, of which, 12 used a placebo group. As for the protocol for laser application, the energy density used ranged from 0.9 to 105 J/cm², while the power density ranged from 9.8 to 500 mW. The number of sessions varied from 1 to 20 and the frequency of applications ranged from daily for 10 days to 1 time per week for 4 weeks. A reduction in pain levels was reported in 13 studies, with 9 of these occurring only in the experimental group, and 4 studies reporting pain relief for both the experimental group and for the placebo. CONCLUSION: Most papers showed that LLLT seemed to be effective in reducing pain from TMD. However, the heterogeneity of the standardization regarding the parameters of laser calls for caution in interpretation of these results. Thus, it is necessary to conduct further research in order to obtain a consensus regarding the best application protocol for pain relief in patients with TMD.