Lippia grata essential oil complexed with ß-cyclodextrin ameliorates biochemical and behavioral deficits in an animal model of progressive parkinsonism.

Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.

Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection.

Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.

(-)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment.

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Volatile profiling and UHPLC-QqQ-MS/MS polyphenol analysis of Passiflora leschenaultii DC. fruits and its anti-radical and anti-diabetic properties.

Twenty-four phenolic compounds including daidzein, epicatechin and artepillin C were identified in Passiflora leschenaultii DC. fruit by UHPLC-QqQ-MS/MS analysis. The aroma profile has been studied using the HS-SPME/GC-MS which revealed 67 volatile compounds including 13 terpenes, 18 alcoholics, 15 esters, ketones and phenolic acids. Further, the proximate composition, anti-radical and anti-diabetic activities of fruit pulp were also determined. The fresh fruit pulp of P. leschenaultii registered higher total phenolic (691.90 mg GAE/g extract) and tannin (313.81 mg GAE/g extract) contents and it also exhibited maximum DPPH (IC50 of 6.69 µg/ml) and ABTS+ (9760.44 µM trolox equivalent/g extract) scavenging activities. The fresh fruit pulp showed a strong inhibition towards the α-Amylase and α-Glucosidase (IC50 of 32.20 and 19.81 µg/mL, respectively) enzymes. Thus, the work stipulates that phenolic compounds rich P. leschenaultii fruit can serve as a potential nutraceutical, antioxidative and anti-diabetic agent in food and pharmaceutical formulations.

Anti-inflammatory and antioxidant activity of carvacrol in the respiratory system: A systematic review and meta-analysis.

Carvacrol is a monoterpene present in the essential oil of a number of plants and has been widely used in traditional medicine because it is considered to have a range of therapeutic effects including in relation to respiratory disease. To conduct a systematic review and meta-analysis to assess the anti-inflammatory and antioxidant activities of carvacrol when used in the treatment of respiratory disorders. A comprehensive literature search using Scopus, MEDLINE-PubMed, Cochrane and Web of Science was undertaken. Papers related to the anti-inflammatory or antioxidant properties of carvacrol in the treatment of an injury in the respiratory system in in vivo studies and published in the period up to and including August 2019. A total of 152 studies were initially identified, with only 17 meeting the inclusion criteria. Five of the studies were performed in humans, and 12 were performed in rodents. Among the 17 studies included in the systematic review, we performed the meta-analysis with nine of the studies with animals. Carvacrol had a positive effect on the reduction of interleukin (IL)-1ß, IL-4, IL-8 and malondialdehyde (MDA); however, the analysis indicated that carvacrol had no effect on IL-6 and tumor necrosis factor alpha (TNF-α), probably due to the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti-inflammatory effects of carvacrol, but its relationship with the reduction of some inflammatory mediators in animals with lung injury needs further elucidation.

Carvacrol suppresses LPS-induced pro-inflammatory activation in RAW 264.7 macrophages through ERK1/2 and NF-kB pathway.

Macrophages are immune system cells that respond to various pathogenic insults. The recognition of antigens is performed through receptors such as TLR4 and RAGE, which recognize pathogen-associated patterns (PAMPs), including lipopolysaccharide (LPS) from Gram-negative bacteria. Carvacrol (CAR) is a phenolic compound found in some essential oils commonly used in folk medicine for treatment of inflammation-related diseases. Previous works observed strong antioxidant actions and some anti-inflammatory effects by CAR in in vivo and in vitro assays. However, the potential pharmacological application of CAR remains limited as details on its mechanisms of action are still missing. Here we investigated the molecular pathways by which CAR acts on LPS-mediated pro-inflammatory activation of RAW 264.7 macrophages. CAR 100 µM protected cells against loss of cell viability induced by LPS (1 µg/mL). Pre-incubation with CAR prevented LPS-induced ERK1/2 phosphorylation, but it had no effect on p38 and JNK activation. The effect of LPS on NF-kB (p65) translocation from cytoplasm to nucleus was inhibited by CAR, as well as NF-kB transcriptional activation. Moreover, LPS-elicited release of TNF-α and IL-1ß were inhibited by CAR, as well as activation of phagocytic activity. Such effects may be related to the antioxidant effect of CAR, as the LPS-induced increase in reactive species (RS) production (assessed by DCFH oxidation) and nitric oxide (NO) production (assessed by nitrite quantification) were inhibited by CAR. Altogether, these results demonstrate that CAR exerts relevant anti-inflammatory actions through a cellular mechanism involving ERK1/2 and NF-kB inhibition and possibly related to the antioxidant properties of this phenolic compound.

Anticonvulsant, sedative, anxiolytic and antidepressant activities of the essential oil of Annona vepretorum in mice: Involvement of GABAergic and serotonergic systems.

Annona vepretorum is an endemic species of the Caatinga biome, known in Northeastern Brazil as "araticum" and/or "pinha da Caatinga". In the present study it was evaluated the neuropharmacological potential of the essential oil obtained from the leaves of Annona vepretorum, as well as of the inclusion complexes of oil obtained with cyclodextrin. Thus, were used neuropharmacological tests already consolidated in the literature like open-field, elevated plus maze, rota-rod, tail suspension test, thiopental-induced sleep test, among others. The acute treatment of essential oil (EO) has anxiolytic, sedative, antiepileptic and antidepressant effects. The anxiolytic and anticonvulsant effects seems to be related to the GABAergic system, probably in the receptor subtypes that mediate the effects of the benzodiazepines, to generate anxiolytic activity. The sedative effect seems to be involved with other signaling pathways. The antidepressant effect of EO seems to be related to its action on serotonergic receptors. It was verified that some behavioral parameters were improved with the oil complexed with ß-cyclodextrin, but this effect was not uniform for all the doses and tests used. Further studies are needed in order to use other options for drug delivery systems. Thus, the essential oil of Annona vepretorum is a promising agent with neurobiological activity and a potential target for drug discovery, since the natural products such as medicinal plants have been a source of new therapeutic proposals.

Evaluation of Aristolochia indica L. and Piper nigrum L. methanol extract against centipede Scolopendra moristans L. using Wistar albino rats and screening of bioactive compounds by high pressure liquid chromatography: a polyherbal formulation.

The present study was aimed to explore the anti-venom activity of Aristolochia indica and Piper nigrum plants against the centipede (Scolopendra moristans) envenomation in animal model. In vtiro phytochemical, antioxidant and blocking of proteolysis were carried out by using standard spectrophotometric methods. In vivo anti-venom activity of methanol extracts was determined using Wistar albino rats after fixing lethal and effective doses. The electrolytes, lipid, liver, kidney, hematological parameters were analyzed and histopathology of skin and liver were also examined. Anti-skin cancer by MTT method and HPLC analysis were also carried out. The CAIPN extract showed higher total phenolics (150.65 ± 0.08 mg GAE/g extract) and flavonoids (158.97 ± 0.93 mg RE/g extract) content. Further, the same extract revealed the higher molybdenum reducing, inhibition of lipid peroxidation (80.08 ± 0.22%), DPPH radical scavenging (3.05 µg/mL), and blocking of proteolysis activities (96.45 ± 0.04%). The parameters like hypersensitivity, electrolytes, lipids, blood components, liver and kidney marker of the CAIPN methanol extract (200 mg/kg) treated envenomated rats was remarkable and same as in the normal animals. Such status was also achieved by RBAI and SPN at 600 mg/kg. The histopathological scoring of skin and liver confirmed the venom neutralizing activity of CAIPN. Also, the CAIPN methanol extract was notable in anti-skin cancer activity (208 µg/mL). The presence of the ferulic acid (04 ± 0.09 µg/mg) and quercetin (35.30 ± 0.30 µg/mg) like compounds was confirmed by HPLC analysis. Hence, the present investigation results conclude that the CAIPN was significant in their action and this polyherbal formulation could be considered as a new source for the pharmaceutical industries to develop a new effective, ecofriendly anti-venom drug.

Analysis of Aloe vera cytotoxicity and genotoxicity associated with endodontic medication and laser photobiomodulation.

This study aims to evaluate, in vitro, the effect of Aloe vera associated with endodontic medication, with or without laser photobiomodulation (FTL) irradiation in FP6 human pulp fibroblasts. The materials were divided into eight groups: CTR - control; CL - FTL alone; AA - Aloe vera with distilled water; AL - Aloe vera with distilled water and FTL; HA - calcium hydroxide P.A. with distilled water; HL - calcium hydroxide P.A. with distilled water and FTL; HAA - calcium hydroxide P.A. with Aloe vera and distilled water; HAL - calcium hydroxide P.A. with Aloe vera, distilled water, and FTL. The cytotoxicity was evaluated by MTT assay at 24, 48, and 72h and the genotoxicity by micronucleus test assay. This study was performed in triplicate. Data obtained in both tests were statistically analyzed by ANOVA and Tukey's tests (p≤0.05). Group AA presented high genotoxicity and low cytotoxicity. After 24, 48, and 72h, the group HAA significantly reduced the cell viability. Interaction with FTL showed slightly increase cell viability after 24 and 48h in groups CL and HL (p<0.001), despite the high genotoxicity in group CL and low genotoxicity in group HL. Group AL showed higher cell survival rate at 72h (p<0.05) and high genotoxicity (p<0.001). It was concluded that Aloe vera allowed higher cell viability in human pulp fibroblasts in the presence of calcium hydroxide or with FTL separately, but genotoxicity increased in these associations.

Phytochemical profile and mechanisms involved in the anti-nociception caused by the hydroethanolic extract obtained from Tocoyena formosa (Cham. & Schltdl.) K. Schum (Jenipapo-bravo) leaves in mice.

Tocoyena formosa, a small ornamental tree growing in the dry regions of central Brazil, is commonly known as 'genipapo do bravo'. This is a medicinal plant traditionally used as an analgesic for rheumatic pain, lower back pain and myalgia, however its use is carried out without scientific evidence, which thus justifies the development of studies to investigate and prove its therapeutic potential. Therefore, the objective of this study was to evaluate the phytochemical profile of Tocoyena formosa (Cham. & Schlecht.) K. Schum (TFLHE) and the mechanisms involved in its anti-nociceptive effect. The TFLHE revealed the presence of gallic acid, catechin, chlorogenic acid, caffeic acid, ellagic acid, rutin, quercetin and luteolin. The TFLHE at doses of 200 and 400mg/kg significantly decreased acetic acid-induced abdominal contortions, the reaction time for the formalin test in both phases and increased the paw withdrawal time in the hot plate thermal stimulus test. The 200mg/kg dose also significantly inhibited the plantar mechanical hyperalgesia intensity induced by formalin within 24h. TREATMENT: with the TFLHE did not cause significant changes in motor performance and coordination in the Rota Rod test. The investigation on the possible mechanism of antinociceptive action of TFLHE indicates the involvement of opioid, glutamatergic, nitric oxide/cGMP and vanilloid systems. It is concluded that the TFLHE has an antinociceptive effect promoted by the aforementioned mechanisms.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. METHODS: We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. CONCLUSION: Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection.

Polyphenols rich Passiflora leschenaultii leaves modulating Farnesoid X Receptor and Pregnane X Receptor against paracetamol-induced hepatotoxicity in rats.

The hepatoprotective effect of P. leschenaultii. (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400mg/kg) were administered daily via gavage for 14days before paracetamol (2000mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed. The assessment revealed that the acetone extract significantly reduced the elevated levels of SGPT, SGOT and ALP in serum. Moreover, the enzymatic antioxidants such as SOD, CAT and LPO were also retained normally by the plant extract. From histopathological analysis, it was clearly evident that the cellular architecture of plant extract treated rat liver tissues were not affected by the paracetamol induction at the higher dose. The results of docking studies also revealed that the identified compounds showed steric interactions (between nonpolar atoms) with amino acid groups. Collectively, the present study suggests that P. leschenaultii leaves extract protects the liver from paracetamol induced hepatic damage.

Effects of luteolin and quercetin 3-ß-d-glucoside identified from Passiflora subpeltata leaves against acetaminophen induced hepatotoxicity in rats.

Passiflora subpeltata has many beneficial effects in the treatment of various diseases including inflammation, pain and fever. This study was aimed to analyze the phytochemical compounds present in acetone extract of P. subpeltata leaves and to evaluate their performance against paracetamol induced hepatotoxicity activity. HPLC-DAD method was used to identify and quantify the phytochemical compounds. Hepatoprotective activity of acetone extract in the treatment of rat liver functions was monitored by the measurement of blood parameters and serum biochemical parameters such as SGOT, SGPT, ALP and in vivo antioxidant parameters viz. SOD, CAT and LPO. Further, liver tissues were also subjected to histopathological analysis. The HPLC-DAD results showed the luteolin and quercetin 3-ß-d-glucoside as newly identified compounds in P. subpeltata species. Pre-treatment with acetone extract of P. subpeltata leaves at 200 and 400mg/kg doses significantly elevated the WBC, RBC and HB counts and retained the serum biochemical and enzymatic antioxidants levels to normal level. Based on this detailed study we conclude that acetone extract of P. subpeltata leaves offered better protection against hepatotoxicity induced by the acetaminophen.

Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice.

BACKGROUND AND AIMS: Shikimic acid (SA) is present in a wide variety of plants and microorganisms used in traditional and folk medicine and also is an essential starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Here, we investigated the anti-inflammatory and antinociceptive actions of isolated SA. METHODS: RAW 264.7 macrophage cells were treated with bacterial LPS (1µg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, and IL-1ß content and MAPK (ERK1/2 and p38) activation was evaluated. Besides, the anti-hyperalgesic actions of SA on in vivo model of mechanical hyperalgesia induced by carrageenan (CG), dopamine (DA), TNF-α and prostaglandin (PGE2) were assessed. RESULTS: In RAW 264.7 cells, SA suppressed LPS-induced decrease in cell viability and nitrite accumulation to control values and inhibited up-regulation of TNF-α (65%) and IL-1ß (39%). These effects may be mediated at least in part by inhibition of LPS-induced ERK 1/2 (22%) and p38 (17%) phosphorylation. In mice, SA at 50, 100, and 200mg/kg decreased formalin-induced nociceptive behavior (around 50%) and inhibited the inflammatory nociception induced by TNF-α and PGE2 (50 to 75% each). Moreover, SA (100 and 200mg/kg) significantly attenuated the mechanical hyperalgesia induced by CG and DA (25 to 40% each). CONCLUSIONS: These results indicate that SA presents anti-inflammatory actions with potential for development of drugs to treat pro-inflammatory and painful conditions.

Acute and sub-acute oral toxicity of Brazilian red propolis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a bee product widely used in folk medicine due to its numerous pharmacological properties. However, samples from different regions can differ in chemical composition, effectiveness, and side effects. Despite the widespread use of Brazilian red propolis, which is an isoflavone-rich variety, its toxicity has not been carefully studied. AIMS OF THE STUDY: To assess the acute and sub-acute toxicity of the hydroethanolic extract of red propolis (HERP) administered orally to rats. MATERIALS AND METHODS: HERP for the acute (300mg/kg) and sub-acute (10, 100 and 200mg/kg) toxicity studies was administered orally to rats according to OECD Guidelines 420 and 407, respectively. Clinical signs were identified, and hematological and biochemical analyses were performed. Water and food uptake as well as body and organ weights of animals were recorded. RESULTS AND CONCLUSIONS: The acute study revealed no lethal effects at 300mg/kg of HERP, but toxic signs were observed, as HERP had an LD50 of more than 300mg/kg, indicating a warning. The most toxic signals in sub-acute studies were observed in males at a dose of 200mg/kg HERP. These results suggest estrogen-like activity, possibly from the isoflavones in HERP.

Use of herbal medicines by elderly patients: A systematic review.

OBJECTIVES: We aimed to survey the published literature for articles that describe the use of herbal supplements by elderly patients and to summarize important aspects of selected studies, including most commonly used supplements, study type, study location, and potential hazards of herbal supplement use. METHODS: Literature searches were conducted on three scientific/medical databases: Medline, Web of Science, and Scopus. Search results were examined for articles involving the use of herbal products in the elderly population that met selection criteria. RESULTS: Initial searches yielded 1297 articles. Of these original results, only 16 met specific selection criteria. Twelve (75%) of studies identified were performed in North America. Nine studies (56.25%) were conducted in the United States. Seven of the studies were cross-sectional (43.8%). The most commonly reported were gingko biloba, garlic, ginseng, aloe vera, chamomile, spearmint, and ginger. Of these, gingko and garlic are the most commonly used among community-dwelling elderly. Both of these supplements have the potential to interact with anticoagulants and produce bruising or bleeding problems. CONCLUSIONS: The use of herbal supplements is common among the elderly, a population that takes a disproportionate share of prescription medications compared to that taken by younger populations. Among the problems uncovered by these studies was a lack of dialog between medical professionals and patients about the use of herbal supplements. Prescribers need to consider the use of herbal supplements and discuss the matter with their elderly patients when making decisions about pharmacological treatments.

Recent Patents on Medicinal Plants/Natural Products as a Therapeutic Approach to Wounds and Burns Healing.

For healing wounds, burns and ulcers has a great impact on economy. New medications, technologies and other interventions are being used for skin injuries and to eliminate infections. Despite several technological and strategic advances in this field, wound care has returned to the roots of medicine and some of the remedies used millennia ago have been studied at present. This review gives an awareness of commercially available drugs to healing of wounds from natural origin. The research was conducted based on the requests for patents deposited in the Espacenet (European Patent Office) and in the WIPO (World Intellectual Property Organization). The research focused on exploring the uses of medicinal plants/natural products as a therapeutic approach to wounds and burns healing. Further, this study discusses the recent trends in the usage of natural products in topical formulations and the patents on it were reviewed, in addition to, future investigations and application of natural products in healing of wounds. Natural products have great therapeutic potential and should be used in the development of new products for the treatment of skin injuries.

Efficacy and safety of medicinal plants or related natural products for fibromyalgia: a systematic review.

To assess the effects of medicinal plants (MPs) or related natural products (RNPs) on fibromyalgia (FM) patients, we evaluate the possible benefits and advantages of MP or RNP for the treatment of FM based on eight randomized placebo-controlled trials (RCTs) involving 475 patients. The methodological quality of all studies included was determined according to JADAD and "Risk of Bias" with the criteria in the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. Evidence suggests significant benefits of MP or RNP in sleep disruption, pain, depression, joint stiffness, anxiety, physical function, and quality of life. Our results demonstrated that MP or RNP had significant effects on improving the symptoms of FM compared to conventional drug or placebo; longer tests are required to determine the duration of the treatment and characterize the long-term safety of using MP, thus suggesting effective alternative therapies in the treatment of pain with minimized side effects.

Morinda citrifolia Linn leaf extract possesses antioxidant activities and reduces nociceptive behavior and leukocyte migration.

Herbal drugs have been used since ancient times to treat a wide range of diseases. Morinda citrifolia Linn (popularly known as "Noni") has been used in folk medicine by Polynesians for over 2,000 years. It is reported to have a broad range of therapeutic effects, including effects against headache, fever, arthritis, gingivitis, respiratory disorders, infections, tuberculosis, and diabetes. The aim of this study was to investigate the antioxidant, anti-inflammatory, antinociceptive, and antibacterial properties of the aqueous extract from M. citrifolia leaves (AEMC). Antioxidant activity was observed against lipid peroxidation, nitric oxide, and hydroxyl radicals. The antinociceptive effect of AEMC was observed in the acetic acid-induced writhing test at the higher dose. Moreover, AEMC significantly reduced the leukocyte migration in doses of 200 and 400 mg/kg and showed mild antibacterial activity. Together, the results suggest that properties of M. citrifolia leaf extract should be explored further in order to achieve newer tools for managing painful and inflammation conditions, including those related to oxidant states.