INTRODUCTION:Cannabidiol (CBD) containing products are available in a plethora of flavors including oral, sublingual, and inhalable forms. Immunotoxicological effects of CBD containing liquids were assessed by hypothesizing that CBD regulates oxidative stress and lipopolysaccharide (LPS) induced inflammatory responses in macrophages, epithelial cells, and fibroblasts.

METHODS:Epithelial cells (BEAS-2B and NHBE), macrophages (U937), and lung fibroblast cells (HFL-1) were treated with varying CBD concentrations or exposed to CBD aerosols and reactive oxygen species (ROS), and the inflammatory mediators, were measured. Furthermore, monocytes and epithelial cells were stimulated with LPS in combination with CBD or dexamethasone to understand the anti-inflammatory effects of CBD.

RESULTS:CBD showed differential effects on IL-8 and MCP-1, and acellular and cellular ROS levels. CBD significantly attenuated LPS-induced NF-κB activity and IL-8 and MCP-1 release from macrophages. Cytokine array data depicted a differential cytokine response due to CBD. Inflammatory mediators, IL-8, serpin E1, CXCL1, IL-6, MIF, IFN-γ, MCP-1, RANTES, and TNF-α were induced, whereas MCP-1/CCL2, CCL5, eotaxin, IL-1ra, and IL-2 were reduced. CBD and dexamethasone treatments reduced the IL-8 level induced by LPS when the cells were treated individually, but showed antagonistic effects when used in combination via MCPIP (monocytic chemotactic protein-induced protein).

CONCLUSION:CBD differentially regulated basal pro-inflammatory response and attenuated both LPS-induced cytokine release and NF-κB activity in monocytes, similar to dexamethasone. Thus, CBD has a differential inflammatory response and acts as an anti-inflammatory agent in pro-inflammatory conditions but acts as an antagonist with steroids, overriding the anti-inflammatory potential of steroids when used in combination.

Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 μM CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFNγ through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPARγ receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2α, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2α induced by LPS/IFNγ. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ERstress pathway is involved in the 'oligoprotective' effects of CBD during inflammation.

Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. However, the mechanisms of these effects are not completely understood. Using the BV-2 mouse microglial cell line and lipopolysaccharide (LPS) to induce an inflammatory response, we studied the signaling pathways engaged in the anti-inflammatory effects of cannabinoids as well as their influence on the expression of several genes known to be involved in inflammation. We found that the two major cannabinoids present in marijuana, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), decrease the production and release of proinflammatory cytokines, including interleukin-1beta, interleukin-6, and interferon (IFN)beta, from LPS-activated microglial cells. The cannabinoid anti-inflammatory action does not seem to involve the CB1 and CB2 cannabinoid receptors or the abn-CBD-sensitive receptors. In addition, we found that THC and CBD act through different, although partially overlapping, mechanisms. CBD, but not THC, reduces the activity of the NF-kappaB pathway, a primary pathway regulating the expression of proinflammatory genes. Moreover, CBD, but not THC, up-regulates the activation of the STAT3 transcription factor, an element of homeostatic mechanism(s) inducing anti-inflammatory events. Following CBD treatment, but less so with THC, we observed a decreased level of mRNA for the Socs3 gene, a main negative regulator of STATs and particularly of STAT3. However, both CBD and THC decreased the activation of the LPS-induced STAT1 transcription factor, a key player in IFNbeta-dependent proinflammatory processes. In summary, our observations show that CBD and THC vary in their effects on the anti-inflammatory pathways, including the NF-kappaB and IFNbeta-dependent pathways.

Significant advances have increased our understanding of the molecular mechanisms of amyotrophic lateral sclerosis (ALS), yet this has not translated into any greatly effective therapies. It appears that a number of abnormal physiological processes occur simultaneously in this devastating disease. Ideally, a multidrug regimen, including glutamate antagonists, antioxidants, a centrally acting anti-inflammatory agent, microglial cell modulators (including tumor necrosis factor alpha [TNF-alpha] inhibitors), an antiapoptotic agent, 1 or more neurotrophic growth factors, and a mitochondrial function-enhancing agent would be required to comprehensively address the known pathophysiology of ALS. Remarkably, cannabis appears to have activity in all of those areas. Preclinical data indicate that cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. In the G93A-SOD1 ALS mouse, this has translated to prolonged neuronal cell survival, delayed onset, and slower progression of the disease. Cannabis also has properties applicable to symptom management of ALS, including analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. With respect to the treatment of ALS, from both a disease modifying and symptom management viewpoint, clinical trials with cannabis are the next logical step. Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.

The roots of the cannabis plant have a long history of medical use stretching back millennia. However, the therapeutic potential of cannabis roots has been largely ignored in modern times.In the first century, Pliny the Elder described inthat a decoction of the root in water could be used to relieve stiffness in the joints, gout, and related conditions. By the 17th century, various herbalists were recommending cannabis root to treat inflammation, joint pain, gout, and other conditions. There has been a subsequent paucity of research in this area, with only a few studies examining the composition of cannabis root and its medical potential. Active compounds identified and measured in cannabis roots include triterpenoids, friedelin (12.8 mg/kg) and epifriedelanol (21.3 mg/kg); alkaloids, cannabisativine (2.5 mg/kg) and anhydrocannabisativine (0.3 mg/kg); carvone and dihydrocarvone;-(-hydroxy--phenylethyl)--hydroxy--cinnamamide (1.6 mg/kg); various sterols such as sitosterol (1.5%), campesterol (0.78%), and stigmasterol (0.56%); and other minor compounds, including choline. Of note, cannabis roots are not a significant source of Δ-tetrahydrocannabinol (THC), cannabidiol, or other known phytocannabinoids.The current available data on the pharmacology of cannabis root components provide significant support to the historical and ethnobotanical claims of clinical efficacy. Certainly, this suggests the need for reexamination of whole root preparations on inflammatory and malignant conditions employing modern scientific techniques.

Skin inflammatory diseases result from complex events that include dysregulation and abnormal expression of inflammatory mediators or their receptors in skin cells. The present study investigates the potential effect of a Cannabis sativa L. ethanolic extract standardized in cannabidiol as antiinflammatory agent in the skin, unraveling the molecular mechanisms in human keratinocytes and fibroblasts. The extract inhibited the release of mediators of inflammation involved in wound healing and inflammatory processes occurring in the skin. The mode of action involved the impairment of the nuclear factor-kappa B (NF-κB) pathway since the extract counteracted the tumor necrosis factor-alpha-induced NF-κB-driven transcription in both skin cell lines. Cannabis extract and cannabidiol showed different effects on the release of interleukin-8 and vascular endothelial growth factor, which are both mediators whose genes are dependent on NF-κB. The effect of cannabidiol on the NF-κB pathway and metalloproteinase-9 (MMP-9) release paralleled the effect of the extract thus making cannabidiol the major contributor to the effect observed. Down-regulation of genes involved in wound healing and skin inflammation wasat least in part due to the presence of cannabidiol. Our findings provide new insights into the potential effect of Cannabis extracts against inflammation-based skin diseases.

ETHNOPHARMACOLOGICAL RELEVANCE:Cannabis sativa L. (C. sativa) is an annual dioecious plant, which shares its origins with the inception of the first agricultural human societies in Asia. Over the course of time different parts of the plant have been utilized for therapeutic and recreational purposes, for instance, extraction of healing oils from seed, or the use of inflorescences for their psychoactive effects. The key psychoactive constituent in C. sativa is calledΔ-9-tetrahydrocannabinol (D9-THC). The endocannabinoid system seems to be phylogenetically ancient, as it was present in the most primitive vertebrates with a neuronal network. N-arachidonoylethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG) are the main endocannabinoids ligands present in the animal kingdom, and the main endocannabinoid receptors are cannabinoid type-1 (CB1) receptor and cannabinoid type-2 (CB2) receptor.

AIM OF THE STUDY:The review aims to provide a critical and comprehensive evaluation, from the ancient times to our days, of the ethnological, botanical, chemical and pharmacological aspects of C. sativa, with a vision for promoting further pharmaceutical research to explore its complete potential as a therapeutic agent.

MATERIALS AND METHODS:This study was performed by reviewing in extensive details the studies on historical significance and ethnopharmacological applications of C. sativa by using international scientific databases, books, Master's and Ph.D. dissertations and government reports. In addition, we also try to gather relevant information from large regional as well as global unpublished resources. In addition, the plant taxonomy was validated using certified databases such as Medicinal Plant Names Services (MPNS) and The Plant List.

RESULTS AND CONCLUSIONS:A detailed comparative analysis of the available resources for C. sativa confirmed its origin and traditional spiritual, household and therapeutic uses and most importantly its popularity as a recreational drug. The result of several studies suggested a deeper involvement of phytocannabinoids (the key compounds in C. sativa) in several others central and peripheral pathophysiological mechanisms such as food intake, inflammation, pain, colitis, sleep disorders, neurological and psychiatric illness. However, despite their numerous medicinal benefits, they are still considered as a menace to the society and banned throughout the world, except for few countries. We believe that this review will help lay the foundation for promoting exhaustive pharmacological and pharmaceutical studies in order to better understand the clinical relevance and applications of non-psychoactive cannabinoids in the prevention and treatment of life-threatening diseases and help to improve the legal status of C. sativa.

Hemp seed (Fructus cannabis) is rich in lignanamides, and initial biological screening tests showed their potential anti-inflammatory and anti-oxidative capacity. This study investigated the possible effects and underlying mechanism of cannabisin F, a hempseed lignanamide, against inflammatory response and oxidative stress in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Cannabisin F suppressed the production and the mRNA levels of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factorα (TNF-α) in a concentration-dependent manner in LPS-stimulated BV2 microglia cell. Furthermore, cannabisin F enhanced SIRT1 expression and blocked LPS-induced NF-κB (Nuclear factor kappa B) signaling pathway activation by inhibiting phosphorylation of IκBα (Inhibit proteins of nuclear factor kappaB) and NF-κB p65. And the SIRT1 inhibitor EX527 significantly inhibited the effect of cannabisin F on pro-inflammatory cytokines production, suggesting that the anti-inflammatory effects of cannabisin F are SIRT1-dependent. In addition, cannabisin F reduced the production of cellular reactive oxygen species (ROS) and promoted the expression of Nrf2 (Nuclear factor erythroid-2 related factor 2) and HO-1 (Heme Oxygenase-1), suggesting that the anti-oxidative effects of cannabisin F are related to Nrf2 signaling pathway. Collectively, these results suggest that the neuro-protection effect ofcannabisin F against LPS-induced inflammatory response and oxidative stress in BV2 microglia cells involves the SIRT1/NF-κB and Nrf2 pathway.

OBJECTIVE: To determine the benefit of cetylated fatty acids (CFA) on knee range of motion and function in patients with osteoarthritis (OA). METHODS: Sixty-four patients with chronic knee OA were evaluated at baseline and at 30 and 68 days after consuming either placebo (vegetable oil; n = 31) or CFA (Celadrin; n = 33). Evaluations included physician assessment, knee range of motion with goniometry, and the Lequesne Algofunctional Index (LAI). RESULTS: After 68 days, patients treated with CFA exhibited significant (p < 0.001) increase in knee flexion (10.1 degrees) compared to patients given placebo (1.1 degrees). Neither group reported improvement in knee extension. Patient responses to the LAI indicated a significant (p < 0.001) shift towards functional improvement for the CFA group (-5.4 points) after 68 days compared to a modest improvement in the placebo group (-2.1 points). CONCLUSION: Compared to placebo, CFA provides an improvement in knee range of motion and overall function in patients with OA of the knee. CFA may be an alternative to the use of nonsteroidal antiinflammatory drugs for the treatment of OA.

Cinnamaldehyde, a bioactive component of cinnamon, is increasingly gaining interest for its preventive and therapeutic effects against metabolic complications like type-2 diabetes. This study is an attempt to understand the effect of cinnamaldehyde in high-fat diet (HFD)-associated increase in fasting-induced hyperphagia and related hormone levels, adipose tissue lipolysis and inflammation, and selected cecal microbial count in mice. Cinnamaldehyde, at 40µM dose, prevented lipid accumulation and altered gene expression toward lipolytic phenotype in 3T3-L1 preadipocyte cell lines. In vivo, cinnamaldehyde coadministration prevented HFD-induced body weight gain, decreased fasting-induced hyperphagia, as well as circulating leptin and leptin/ghrelin ratio. In addition to that, cinnamaldehyde altered serum biochemical parameters related to lipolysis, that is, glycerol and free fatty acid levels. At transcriptional level, cinnamaldehyde increased anorectic gene expression in hypothalamus and lipolytic gene expression in visceral white adipose tissue. Furthermore, cinnamaldehyde also decreased serum IL-1β and inflammatory gene expression in visceral white adipose tissue. However, cinnamaldehyde did not modulate the population of selected gut microbial (Lactobacillus, Bifidibaceria, and Roseburia) count in cecal content. In conclusion, cinnamaldehyde increased adipose tissue lipolysis, decreased fasting-induced hyperphagia, normalized circulating levels of leptin/ghrelin ratio, and reduced inflammation in HFD-fed mice, which augurs well for its antiobesity role.

The healthy benefits of hemp (L.) seed have often been attributed to its oils and proteins. Recent studies reveal that hemp seed phenylpropionamides could also show various bioactivities. Continuation of our study on hemp seed provided a phenylpropionamide, coumaroylaminobutanol glucopyranoside (CLG). This work investigated the neuroprotective effect of CLG and its underlying mechanism using lipopolysaccharide-induced BV2 microglia. Our study demonstrated that CLG increased adenosine monophosphate-activated protein kinase (AMPK) expression, suppressed the nuclear factor-kappa B (NF-κB) signaling pathway by inhibiting the phosphorylation of IκBα and NF-κB p65 and decreased proinflammatory cytokine levels in a concentration-dependent manner. Furthermore, CLG reduced the production of cellular reactive oxygen species and stimulated the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway. Collectively, these results suggested that CLG effectively and simultaneously inhibited inflammatory responses and oxidative stress through the NF-κB and Nrf-2 signaling pathways. AMPK was also involved in the anti-inflammatory effect of CLG. This study provides new insights into the diverse bioactive constituents of hemp seed.

This study aimed to investigate the effects of electroacupuncture at the Lieque, Chize, and Zusanli points in patients with lung injury caused by severe acute pancreatitis. Patients with acute respiratory distress syndrome (ARDS) induced by severe acute pancreatitis (SAP) were randomly divided into three groups based on the treatment: conventional therapy alone (group A), electroacupuncture of nonacupoints with conventional therapy (group B), and electroacupuncture at the Lieque (LU7), Chize (LU5), and Zusanli (ST36) points (group C) once a day for 5 days. Arterial blood samples were obtained for blood gas analysis before electroacupuncture (T1) and 3 (T2) and 5 (T3) days after electroacupuncture. The oxygenation index was significantly higher in all groups at T2 and T3 than that at T1, while the APACHE-II scores were decreased significantly. The expression of TNF-α was significantly decreased and the IL-10 was significantly increased in all groups at T3. The oxygenation index at T2 and T3 was significantly higher in group C than that in group B. Electroacupuncture at Lieque, Chize, and Zusanli can lessen the lung injury induced by SAP, and the mechanism maybe related to the decreased TNF-α and increased IL-10 value. Clinical Registration Number is ChiCTR-ICR-15006850.

OBJECTIVE:To investigate the therapeutic effects of acupuncture combined with nerve block for treatment of lumbar disc herniation.

METHODS:Ninety cases of lumbar disc herniation were randomly divided into three groups: acupuncture combined with nerve block group, acupuncture group and nerve block group, 30 cases in each group. The acupuncture combined with nerve block group was treated with acupuncture combined with nerve block therapy, L2-L5 Jiaji (EX-B 2), Zhibian (BL 54), Huantiao (GB 30), Yanglingquan (GB 34) etc. were selected for acupuncture, affected nerve root, sciatic nerve or common peroneal nerve were selected for nerve block with anti-inflammation-analgesic injection; the acupuncture group was treated with acupuncture only; the nerve block group was treated with nerve block only. After 4 weeks of treatment, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI) and modified MacNab standard were compared to evaluate the therapeutic effects of three groups.

RESULTS:The VAS and ODI in all groups were significantly decreased after one week, two weeks and four weeks of treatment (all P<0.01); after one week of treatment, the scores of VAS and ODI in nerve block group and acupuncture combined with nerve block group were significantly lower than those of acupuncture group (P<0.05); after two weeks and four weeks of treatment, the scores of VAS and ODI in acupuncture combined with nerve block group were significantly lower than those of acupuncture group and nerve block group (P<0.05). The effective rate and excellent and good rate of the acupuncture combined with nerve block group were significantly higher than those of acupuncture group and nerve block group (both P<0.01).

CONCLUSION:The nerve block therapy and acupuncture are effective methods for treatment of lumbar disc herniation, while it has a better effect when these two treatments are combined used.

OBJECTIVE:To investigate the therapeutic effects of acupuncture combined with nerve block for treatment of lumbar disc herniation.

METHODS:Ninety cases of lumbar disc herniation were randomly divided into three groups: acupuncture combined with nerve block group, acupuncture group and nerve block group, 30 cases in each group. The acupuncture combined with nerve block group was treated with acupuncture combined with nerve block therapy, L2-L5 Jiaji (EX-B 2), Zhibian (BL 54), Huantiao (GB 30), Yanglingquan (GB 34) etc. were selected for acupuncture, affected nerve root, sciatic nerve or common peroneal nerve were selected for nerve block with anti-inflammation-analgesic injection; the acupuncture group was treated with acupuncture only; the nerve block group was treated with nerve block only. After 4 weeks of treatment, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI) and modified MacNab standard were compared to evaluate the therapeutic effects of three groups.

RESULTS:The VAS and ODI in all groups were significantly decreased after one week, two weeks and four weeks of treatment (all P<0.01); after one week of treatment, the scores of VAS and ODI in nerve block group and acupuncture combined with nerve block group were significantly lower than those of acupuncture group (P<0.05); after two weeks and four weeks of treatment, the scores of VAS and ODI in acupuncture combined with nerve block group were significantly lower than those of acupuncture group and nerve block group (P<0.05). The effective rate and excellent and good rate of the acupuncture combined with nerve block group were significantly higher than those of acupuncture group and nerve block group (both P<0.01).

CONCLUSION:The nerve block therapy and acupuncture are effective methods for treatment of lumbar disc herniation, while it has a better effect when these two treatments are combined used.

From last decade, there has been progressive improvement in computational drug designing. Several diseases are being cured from different plant extracts and products. Rheumatoid arthritis (RA) is the most shared disease among auto-inflammatory diseases. Tumor necrosis factor (TNF)-α is associated with RA pathway and has adverse effects. Extensive literature review showed that plant species under study (Cannabis sativa, Prunella vulgaris and Withania somnifera) possess anti-inflammatory, anti-arthritic and anti-rheumatic properties. 13 anti-inflammatory compounds were characterized and filtered out from medicinal plant species and analyzed for RA by targeting TNF-α through in silico analyses. By using ligand based pharmacophore generation approach and virtual screening against natural products libraries we retrieved twenty unique molecules that displayed utmost bindingaffinity, least binding energies and effective drug properties. The docking analyses revealed that Ala-22, Glu-23, Ser-65, Gln-67, Tyr-141, Leu-142, Asp-143, Phe-144 and Ala-145 were critical interacting residues for receptor-ligand interactions. It is proposed that the RA patients should use reported compounds for the prescription of RA by targeting TNF-α. This report is opening new dimensions for designing innovative therapeutic targets to cure RA.

Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

Coriolus versicolor (CV) is a traditional medicine and food mushroom. Our previous study demonstrated that CV extract exhibited anti-hyperglycemia and anti-insulin resistance effects. However, the effect of CV on cardiac function in diabetic cardiomyopathy (DCM) remains unclear. Therefore, we aimed to investigate the effect of CV on cardiac function in diabetes mellitus (DM) rats. We found that the cardiac dysfunction of DM rats was markedly improved by CV extract treatment. CV extract administration significantly attenuated cardiac fibrosis in DM rats, which was accompanied by suppressed transforming growth factor beta 1 (TGF-β1)/Smad signaling as indicated by decreased levels of TGF-β1, p-Smad2, and p-Smad3 and increased Smad7 expression. Moreover, CV extract treatment significantly alleviated cardiac inflammation as shown by decreased levels of NLRP3 receptor, cleaved caspase-1, IL-1β, and IL-18 in DM rats at leastpartly due to the inhibition of the NF-κB. In addition, high-glucose treatment induced cardiac fibrosis and increased cardiac inflammation in cardiac fibroblast cells, but these effects were ameliorated by CV extract treatment. Therefore, we conclude that the protective effect of CV on DCM is associated with the suppression of TGF-β1/Smad signaling and attenuation of NLRP3 inflammasome activation, suggesting that CV extract may be a potential therapeutic agent for DCM.

This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death. Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation.

OBJECTIVE:Mushroom crude polysaccharides offer a complete package of various medicinal activities. In this context, the present study aimed to unveil structural and biomedical properties of crude polysaccharide (MLHWP) obtained from an edible wild mushroom Macrocybe lobayensis (R. Heim) Pegler&Lodge.

METHOD:Chemical characterization was accomplished with the help of spectrophotometry, Fourier-transform infrared spectroscopy, HPTLC and GC-MS. Immunomodulatory activity of the crude polysaccharide and its signalling mechanism was assessed using RAW 264.7 cells. Furthermore, antioxidant activity was analysed based on radical scavenging, metal ion chelating and reducing effect.

KEY FINDINGS:Compositional study revealed that MLHWP possessed triple helical structure and its backbone consisted ofβ-linked glucan along with xylose, rhamnose, mannose and galactose. Investigation on bioactive potency revealed that MLHWP augmented macrophage activity in terms of viability, phagocytosis, NO and ROS generation. Gene expression studies indicated that MLHWP signalled through TLR and modulated expression of immunomodulation-related genes including NF-κB, COX-2, IFN-γ, TNF-α, iNOS and Iκ-βα. Besides, MLHWP displayed noticeable antioxidant potential as reflected in all investigating assays.

CONCLUSIONS:Overall, the results portrayed possibility of MLHWP as pharmaceutical agent with multidimensional application.

The aim of this article was to review current evidence about cryotherapy in inflammatory rheumatic diseases (therapeutic and biological effects). For therapeutic effects, we performed a systematic review (PubMed, EMBASE, Cochrane Library, LILACS databases, unpublished data) and selected studies including non-operated and non-infected arthritic patients treated with local cryotherapy or whole-body cryotherapy. By pooling 6 studies including 257 rheumatoid arthritis (RA) patients, we showed a significant decrease in pain visual analogic scale (mm) and 28-joint disease activity score after chronic cryotherapy in RA patients. For molecular pathways, local cryotherapy induces an intrajoint temperature decrease, which might downregulate several mediators involved in joint inflammation and destruction (cytokines, cartilage-degrading enzymes, proangiogenic factors), but studies in RA are rare. Cryotherapy should be included in RA therapeutic strategies as an adjunct therapy, with potential corticosteroid and nonsteroidal anti-inflammatory drug dose-sparing effects. However, techniques and protocols should be more precisely defined in randomized controlled trials with stronger methodology.