Effects of Iranian herbal Zofa® syrup for the management of clinical symptoms in patients with COVID-19: A randomized clinical trial.

Objective: The objective of this study was to determine the role of Iranian herbal Zofa® syrup in improving the clinical symptoms of patients with COVID-19. Materials and Methods: This randomized clinical trial was conducted on 105 patients with COVID-19. Patients were randomly assigned to the intervention (n=35) group (received 10 ml of Zofa® syrup every 8 hours/seven days plus standard treatment) or the control (n=70) group (received only standard treatment). Assessments were performed before and after treatment. Results: The groups were comparable regarding age (p=0.980), gender (p=0.584), comorbidities (p=0.318), or drug history (p=0.771). There was no difference between patients' recovery status at the time of discharge (p=0.327) or two weeks post-discharge (p=0.165) in the intervention and control groups. No patient was hospitalized to the intensive care unit (ICU) for supplemental oxygen therapy and no patient died in the intervention group. However, in the control group, three (4.5%) patients were transferred to the ICU, and two (3.03%) patients died. Conclusion: Considering the better recovery status of the patients at the time of discharge and the absence of patient deaths in the intervention group, more additional studies are needed to confirm these findings and elucidate the role of Zofa® in COVID-19.

Medicinal plants for the treatment of neuropathic pain: A review of randomized controlled trials.

Neuropathic pain is a disabling condition caused by various diseases and can profoundly impact the quality of life. Unfortunately, current treatments often do not produce complete amelioration and can be associated with potential side effects. Recently, herbal drugs have garnered more attention as an alternative or a complementary treatment. In this article, we summarized the results of randomized clinical trials to evaluate the effects of various phytomedicines on neuropathic pain. In addition, we discussed their main bioactive components and potential mechanisms of action to provide a better view of the application of herbal drugs for treating neuropathic pain.

Spices and Biomarkers of COVID-19: A Mechanistic and Therapeutic Perspective.

In the face of the COVID-19 pandemic, many people around the world have increased their healthy behaviors to prevent transmission of the virus and potentially improve their immune systems. Therefore, the role of diet and food compounds such as spices with bioactive and antiviral properties may be important in these efforts. In this chapter, we review the efficacy of spices such as turmeric (curcumin), cinnamon, ginger, black pepper, saffron, capsaicin, and cumin by investigating the effects of these compounds of COVID-19 disease severity biomarkers.

Phytochemicals as substances that affect astrogliosis and their implications for the management of neurodegenerative diseases.

Astrocytes are a multifunctional subset of glial cells that are important in maintaining the health and function of the central nervous system (CNS). Reactive astrocytes may release inflammatory mediators, chemokines, and cytokines, as well as neurotrophic factors. There may be neuroprotective (e.g., cytokines, like IL-6 and TGF-b) and neurotoxic effects (e.g., IL-1ß and TNF-a) associated with these molecules. In response to CNS pathologies, astrocytes go to a state called astrogliosis which produces diverse and heterogenic functions specific to the pathology. Astrogliosis has been linked to the progression of many neurodegenerative disorders. Phytochemicals are a large group of compounds derived from natural herbs with health benefits. This review will summarize how several phytochemicals affect neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Parkinson's disease) in basic medical and clinical studies and how they might affect astrogliosis in the process.

An Investigation into the Effects of Chemical, Pharmaceutical, and Herbal Compounds on Neuroglobin: A Literature Review.

Neuroglobin (Ngb) is an oxygen-binding globin protein that is mainly expressed in the neurons of the central and peripheral nervous system. However, moderate levels of Ngb have also been detected in non-neural tissues. Ngb and Ngb modulating factors have been increasingly studied over the last decade due to their neuroprotective role in neurological disorders and hypoxia. Studies have shown that a number of chemicals, pharmaceuticals, and herbal compounds can modulate the expression of Ngb at different dose levels, indicating a protective role against neurodegenerative diseases. Iron chelators, hormones, antidiabetic drugs, anticoagulants, antidepressants, plant derivatives and short-chain fatty acids are among these compounds. Therefore, this study aimed to review the literature focused on the possible effects and mechanisms of chemical, pharmaceutical, and herbal compounds on Ngbs.

Modulatory properties of curcumin in cancer: A narrative review on the role of interferons.

The immune network is an effective network of cell types and chemical compounds established to maintain the body's homeostasis from foreign threats and to prevent the risk of a wide range of diseases; hence, its proper functioning and balance are essential. A dysfunctional immune system can contribute to various disorders, including cancer. Therefore, there has been considerable interest in molecules that can modulate the immune network. Curcumin, the active ingredient of turmeric, is one of these herbal remedies with many beneficial effects, including modulation of immunity. Curcumin is beneficial in managing various chronic inflammatory conditions, improving brain function, lowering cardiovascular disease risk, prevention and management of dementia, and prevention of aging. Several clinical studies have supported this evidence, suggesting curcumin to have an immunomodulatory and anti-inflammatory function; nevertheless, its mechanism of action is still not clear. In the current review, we aim to explore the modulatory function of curcumin through interferons in cancers.

A review on curcumin colon-targeted oral drug delivery systems for the treatment of inflammatory bowel disease.

Synthetic drugs and monoclonal antibodies are the typical treatments to combat inflammatory bowel disease (IBD). However, side effects are present when these treatments are used, and their continued application could be restricted by the high relapse rate of the disease. One potential alternative to these treatments is the use of plant-derived products. The use curcumin is one such treatment option that has seen an increase in usage in treating IBD. Curcumin is derived from a rhizome of turmeric (Curcuma longa), and the results of studies on the use of curcumin to treat IBD are promising. These studies suggest that curcumin interacts with cellular targets such as NF-κB, JAKs/STATs, MAPKs, TNF-α, IL-6, PPAR, and TRPV1 and may reduce the progression of IBD. Potentially, curcumin can be used as a therapeutic agent for patients with IBD when it reduces the incidence of clinical relapse. This review discusses the strategies utilized in designing and developing an oral colonic delivery dosage form of curcumin.

Curcumin-piperine co-supplementation and human health: A comprehensive review of preclinical and clinical studies.

Curcumin is extracted from the rhizomes Curcuma longa L. It is known for its anti-inflammatory and anti-oxidant activities. Despite its safety and potential for use against various diseases, curcumin's utility is restricted due to its low oral bioavailability. Co-administration of curcumin along with piperine could potentially improve the bioavailability of curcumin. The present review aimed to provide an overview of the efficacy and safety of curcumin-piperine co-supplementation in human health. The findings of this comprehensive review show the beneficial effects of curcumin-piperine in improving glycemic indices, lipid profile and antioxidant status in diabetes, improving the inflammatory status caused by obesity and metabolic syndrome, reducing oxidative stress and depression in chronic stress and neurological disorders, also improving chronic respiratory diseases, asthma and COVID-19. Further high-quality clinical trial studies are needed to firmly establish the clinical efficacy of the curcumin-piperine supplement.

Probiotics as an Adjuvant for Management of Gastrointestinal Cancers through their Anti-inflammatory Effects: A Mechanistic Review.

The immune system's role in maintaining the health of the gastrointestinal (GI) system is like a double-edged sword. Simultaneously, it could reduce the risk of pathogen invasion by the inflammatory response. However, if regulated improperly, it could also propagate oncogenic signaling that transfers a normal cell into the malignant counterpart. Thus, several mechanisms have been proposed, such as the immune system could disturb the GI homeostasis and increase the survival and proliferative capacity of cells, leading to the formation of a wide range of malignancies. Among the endless list of these mechanisms, inflammatory responses are currently fascinating research areas, as this response regulation is by the gut microbiota. Given this, microbiota manipulation might be a convenient and efficient way to prevent GI cancer. Probiotics could potentially achieve this by overturning the milieu in favor of normal gut homeostasis. In addition to the safety of the use of probiotics, along with their potential ability to interact with immune system responses, these bacteria are also being analyzed from the perspective of dietary supplements. In the present review, we aimed to look into the mechanisms through which probiotics modulate immune response to stimulate anti-inflammatory responses and promote immune surveillance against neoplastic cells.

Protective effects of curcumin on ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a term used to describe phenomena connected to the dysfunction of various tissue damage due to reperfusion after ischemic injury. While I/R may result in systemic inflammatory response syndrome or multiple organ dysfunction syndrome, there is still a long way to improve therapeutic outcomes. A number of cellular metabolic and ultrastructural alterations occur by prolonged ischemia. Ischemia increases the expression of proinflammatory gene products and bioactive substances within the endothelium, such as cytokines, leukocytes, and adhesion molecules, even as suppressing the expression of other "protective" gene products and substances, such as thrombomodulin and constitutive nitric oxide synthase (e.g., prostacyclin, nitric oxide [NO]). Curcumin is the primary phenolic pigment derived from turmeric, the powdered rhizome of Curcuma longa. Numerous studies have shown that curcumin has strong antiinflammatory and antioxidant characteristics. It also prevents lipid peroxidation and scavenges free radicals like superoxide anion, singlet oxygen, NO, and hydroxyl. In our study, we highlight the mechanisms of protective effects of curcumin against I/R injury in various organs.

Anticancer Mechanisms of Berberine: A Good Choice for Glioblastoma Multiforme Therapy.

The most typical malignant brain tumor, glioblastoma multiforme (GBM), seems to have a grim outcome, despite the intensive multi-modality interventions. Literature suggests that biologically active phytomolecules may exert anticancer properties by regulating several signaling pathways. Berberine, an isoquinoline alkaloid, has various pharmacological applications to combat severe diseases like cancer. Mechanistically, it inhibits cell proliferation and invasion, suppresses tumor angiogenesis, and induces cell apoptosis. The antitumoral effect of berberine in GBM is increasingly recognized. This review sheds new light on the regulatory signaling mechanisms of berberine in various cancers, proposing its potential role as a therapeutic agent for GBM.

The effects of phytochemicals and herbal bio-active compounds on tumour necrosis factor-α in overweight and obese individuals: a clinical review.

Obesity is abnormal fat accumulation in the body which acts as a risk factor for various cardiometabolic states. Adipose tissue in excess can release inflammatory factors, including TNF-α and IL-6, and suppress adiponectin production. TNF-α increases the levels of IL-6 and acute phase reactants such as C-reactive protein. Inflammation has a crucial role in developing and progressing various cardiometabolic diseases and a wide range of obesity-related complications. It has been shown that TNF-α has a significant role in the development of insulin resistance. Recently, a growing body of evidence has focused on herbal medicine, phytochemicals and natural bioactive compounds as inexpensive, relatively easy accessible agents with low adverse effects to reduce inflammatory markers such as TNF-α and simultaneously decrease insulin resistance, glucose intolerance, and dyslipidemia in obesity. The main focus of the current review is to summarize the results of the studies, which assessed the effects of phytochemicals and herbal bio-active compounds on serum TNF-α in subjects with overweight or obesity. This review suggests that herbal medicine have favorable effects on the reduction of TNF-α concentration; however, the results were not uniform for different products. Among the reviewed plants, ginger, ginseng, resveratrol, and flaxseed had more promising effects.

Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials.

It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration. CRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings.

PLGA-Based Curcumin Delivery System: An Interesting Therapeutic Approach in the Treatment of Alzheimer's Disease.

Progressive degeneration and dysfunction of the nervous system because of oxidative stress, aggregations of misfolded proteins, and neuroinflammation are the key pathological features of neurodegenerative diseases. Alzheimer's disease is a chronic neurodegenerative disorder driven by uncontrolled extracellular deposition of ß-amyloid (Aß) in the amyloid plaques and intracellular accumulation of hyperphosphorylated tau protein. Curcumin is a hydrophobic polyphenol with noticeable neuroprotective and anti-inflammatory effects that can cross the blood-brain barrier. Therefore, it is widely studied for the alleviation of inflammatory and neurological disorders. However, the clinical application of curcumin is limited due to its low aqueous solubility and bioavailability. Recently, nano-based curcumin delivery systems are developed to overcome these limitations effectively. This review article discusses the effects and potential mechanisms of curcumin-loaded PLGA nanoparticles in Alzheimer's disease.

The effects of herbal medicines on cancer therapy-induced oral mucositis: A literature review.

Cancer therapy-induced oral mucositis (OM) is one of the most troublesome morbidities after radio-chemotherapy. Age, nutritional status, tumor type, oral hygiene, and treatment method are the determinants for OM incidence. In addition, oxygen-free radicals can act as a trigger for an inflammatory milieu that causes OM. Based on the debilitating nature of OM, finding a safe and inexpensive agent with anti-inflammatory, anti-microbial, and antioxidative properties can be valuable for this situation. Considering the harmful effects of some chemical agents, herbal medicine has been suggested as a potential alternative owing to unique properties such as safety, availability and low cost. Many studies have illustrated several pharmacological properties of herbal medicines in recent years, such as anti-inflammatory, anti-microbial, and antioxidative activities, which are essential factors in the palliation of cancer therapy-induced OM. This review aimed to evaluate herbal medicines' effects on cancer therapy-induced OM. According to this comprehensive review, it is concluded that medicinal plants and phytochemicals can be used as practical agents in the palliation of cancer therapy-induced OM without any serious side effects.

The involvement of JAK/STAT signaling pathway in the treatment of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder in which inflammation and oxidative stress play key etiopathological role. The pathology of PD brain is characterized by inclusions of aggregated α-synuclein (α-SYN) in the cytoplasmic region of neurons. Clinical evidence suggests that stimulation of pro-inflammatory cytokines leads to neuroinflammation in the affected brain regions. Upon neuroinflammation, the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway, and other transcription factors such as nuclear factor κB (NF-κB), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), mammalian target of rapamycin (mTOR), and toll-like receptors (TLRs) are upregulated and induce the microglial activation, contributing to PD via dopaminergic neuron autophagy. Aberrant activation or phosphorylation of the components of JAK/STAT signaling pathway has been implicated in increased transcription of the inflammation-associated genes and many neurodegenerative disorders such as PD. Interferon gamma (IFN-γ), and interleukine (IL)-6 are two of the most potent activators of the JAK/STAT pathway, and it was shown to be elevated in PD. Stimulation of microglial cell with aggregated α-SYN results in production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and IL-1ß in PD. Dysregulation of the JAK/STAT in PD and its involvement in various inflammatory pathways make it a promising PD therapy approach. So far, a variety of synthetic or natural small-molecule JAK inhibitors (Jakinibs) have been found promising in managing a spectrum of ailments, many of which are in preclinical research or clinical trials. Herein, we provided a perspective on the function of the JAK/STAT signaling pathway in PD progression and gathered data that describe the rationale evidence on the potential application of Jakinibs to improve neuroinflammation in PD.

Effect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trials.

We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = -0.40 mg/L; 95% CI: -0.70 to -0.09 mg/L; p = .01) and CRP (MWD = -0.31 mg/L; 95% CI: -0.47 to -0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = -0.48 mg/L; 95% CI: -0.92 to -0.04 mg/L; p = .03) and CRP (WMD = -0.47 mg/L, 95% CI = -0.69 to -0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day.

The Effect of Curcumin Supplemsentation on Anthropometric Indices in Overweight and Obese Individuals: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Curcumin is an active molecule present in turmeric and is the main therapeutic compound. There is growing evidence that curcumin could affect various anthropometric indices. We performed a systematic review to evaluate the efficacy of curcumin supplementation on anthropometric indices in obese and overweight individuals. METHODS: A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Google Scholar from inception up to February 2020 to identify randomized controlled trials investigating the effect of curcumin supplementation on anthropometric indices including body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), arm circumference (AC), waist-hip ratio (WHR), total body fat (TBF), and visceral fat (VF) in obese and overweight individuals. The Jadad scale was used to assess the quality of the included studies. RESULT: Twenty-eight randomized controlled trials, comprising 2168 participants, were included in the systematic review. The results of 16 papers indicated that curcumin reduced at least one of the anthropometric indices among individuals with a BMI ≥ 25 kg/m2. Nevertheless, 12 articles showed that curcumin supplementation was not effective in any of the measured anthropometric factors. The included trials exhibited substantial heterogeneity in terms of the treatment protocol, follow-up duration, curcumin dosage, and background diseases of the participants. CONCLUSION: Clinical trials that have independently examined the effects of curcumin in obese or overweight individuals are limited. However, available studies indicate that curcumin has beneficial impacts on various anthropometric indices. Further trials with longer duration of interventions are needed to confirm these findings.

The Effect of Curcumin in Improving Lipid Profile in Patients with Cardiovascular Risk Factors: A Systematic Review of Clinical Trials.

Cardiovascular disease (CVD) is a major cause of death worldwide. Lipid abnormalities are one of the major risk factors for CVD. Curcumin is a natural polyphenol with lipid-lowering properties. Therefore, we carried out a systematic review to summarize the randomized controlled trials (RCTs) investigating the effect of curcumin on lipid profile in patients at risk of CVD. A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar up to March 1, 2020, to identify controlled clinical trials assessing the effects of curcumin on lipid profile in patients at risk of CVD. From 1051 initially identified studies, 22 met the eligibility criteria. Curcumin supplementation significantly reduced at least one of the lipid profile indices (triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol) in 15 studies and improved more than one index in five studies. However, curcumin had no effect on any of lipid profile indices in seven studies. Overall, studies using a bioavailable formulation of curcumin had a better impact on the lipid profile. The findings of this systematic review showed that curcumin supplementation significantly reduced at least one of the lipid profile indices in more than two-thirds of the included studies. Curcumin might be used as an accessible, inexpensive, and safe agent to reduce risk of CVD. More randomized, clinical controlled trials are needed to verify these results.

The Effects of Curcumin in the Treatment of Gingivitis: A Systematic Review of Clinical Trials.

Different modalities of treatments are available for management of gingival disease but most have adverse effects. Curcumin has anti-inflammatory properties and can be used for management of various inflammatory processes. This systematic review evaluates the effects of curcumin as an adjuvant to oral hygiene on plaque index (PI), gingival index (GI), gingival bleeding index (GBI), and inflammation in patients with gingivitis. A comprehensive search was conducted using PubMed/MEDLINE, Cochrane, SCOPUS, and Google Scholar. Based on the Population, Intervention, Control, and Outcome (PICO) model, clinical trials which tested the effects of curcumin as an adjunctive product or alone in control of gingival inflammation up until 21 February 2020 with language restrictions were selected. From the 422 papers found, 14 met the eligibility criteria. In most of these studies, curcumin treatment achieved significant reductions in PI, GI, GBI, and microbial colony count and was as effective as chlorhexidine mouthwash, with no serious adverse effects. We conclude that treatment with curcumin for gingivitis is safe as a natural herbal compound and is as effective as chlorhexidine mouthwash.