Used in Southeast Asia for generations, kratom gained popularity in the United States and elsewhere over the past several decades. Derived from Mitragyna speciosa, kratom preparations including leaves, teas, powders, capsules, and extracts may yield stimulant, analgesic, and opioid-like effects that occur dose-dependently based on concentrations of kratom\'s key alkaloids, mitragynine and 7-hydroxymitragynine. Such effects are responsible for kratom\'s potential as a reduced-harm alternative to opiates and as a withdrawal treatment. But these properties are also associated with tolerance development and addictive potential. Given mitragynine and 7-hydroxymitragynine activity on cytochrome P450 isoforms and opioid receptors, adverse effects among polysubstance users are a concern. Current literature on the toxicology of kratom is reviewed, including product alkaloid concentrations, in vitro and in vivo data, epidemiological evidence, and human case data. The potential harms and benefits of kratom products are discussed within an exposure assessment framework, and recommendations for industry are presented. Current evidence indicates that kratom may have therapeutic potential in some persons and that products present few risks with typical, non-polysubstance use. However, few studies identified alkaloid doses at which adverse effects were expected in humans or animals. Such research is needed to inform future assessments of kratom\'s risks and benefits.

Cancer refers to the proliferation and multiplication of aberrant cells inside the human body, characterized by their capacity to proliferate and infiltrate various anatomical regions. Numerous biochemical pathways and signaling molecules have an impact on the cancer auto biogenesis process. The regulation of crucial cellular processes necessary for cell survival and proliferation, which are triggered by phytochemicals, is significantly influenced by signaling pathways. These pathways or components are regulated by phytochemicals. Medicinal plants are a significant reservoir of diverse anticancer medications employed in chemotherapy. The anticancer effects of phytochemicals are mediated by several methods, including induction of apoptosis, cessation of the cell cycle, inhibition of kinases, and prevention of carcinogenic substances. This paper analyzes the phytochemistry of seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, and saponins, focusing on the involvement of the MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, and actin dynamics. Hence, this review has examined a range of phytochemicals, encompassing their structural characteristics and potential anticancer mechanisms. It has underscored the significance of plant-derived bioactive compounds in the prevention of cancer, utilizing diverse molecular pathways. In addition, this endeavor also seeks to incentivize scientists to carry out clinical trials on anticancer medications derived from plants.

BACKGROUND: According to the World Health Organization, more than 80% of the world\'s population relies on traditional medicine. Traditional medicine is typically based on the use of single herbal drugs or polyherbal formulations (PHFs) to manage diseases. However, the probable mode of action of these formulations is not well studied or documented. Over the past few decades, computational methods have been used to study the molecular mechanism of phytochemicals in single herbal drugs. However, the in silico methods applied to study PHFs remain unclear.
OBJECTIVE: The aim of this protocol is to develop a search strategy for a scoping review to map the in silico approaches applied in understanding the activity of PHFs used as traditional medicines worldwide.
METHODS: The scoping review will be conducted based on the methodology developed by Arksey and O\'Malley and the recommendations of the Joanna Briggs Institute (JBI). A set of predetermined keywords will be used to identify the relevant studies from five databases: PubMed, Embase, Science Direct, Web of Science, and Google Scholar. Two independent reviewers will conduct the search to yield a list of relevant studies based on the inclusion and exclusion criteria. Mendeley version 1.19.8 will be used to remove duplicate citations, and title and abstract screening will be performed with Rayyan software. The JBI System for the Unified Management, Assessment, and Review of Information tool will be used for data extraction. The scoping review will be reported based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines.
RESULTS: Based on the core areas of the scoping review, a 3-step search strategy was developed. The initial search produced 3865 studies. After applying filters, 875 studies were short-listed for further review. Keywords were further refined to yield more relevant studies on the topic.
CONCLUSIONS: The findings are expected to determine the extent of the knowledge gap in the applications of computational methods in PHFs for any traditional medicine across the world. The study can provide answers to open research questions related to the phytochemical identification of PHFs, criteria for target identification, strategies applied for in silico studies, software used, and challenges in adopting in silico methods for understanding the mechanisms of action of PHFs. This study can thus provide a better understanding of the application and types of in silico methods for investigating PHFs.
UNASSIGNED: PRR1-10.2196/56646.

OBJECTIVE: Periodontal disease is a chronic condition caused by microbial infection and mediated by the host\'s immune response. Phytotherapy is a therapeutic approach that utilizes a renewable resource capable of supplying less expensive medicines for the world\'s growing population. This review aimed to present clinical evidence on the use of complementary medicinal herbs in the treatment of periodontal diseases.
METHODS: Different databases were searched using the terms \"herbal\" and \"periodontitis.\" All included studies were examined with a focus on herbal indications, type, and prescription length. Dentists\' therapeutic and prophylactic herbal prescribing habits were also assessed.
RESULTS: Various herbs such as turmeric, neem, aloe-vera, pomegranate, catechu, tulsi, cloves, lemon grass, green tea, tea tree oil, peppermint, garlic, pineapple, oak bark, babul, bakul, sage, coriander, moringa, amla, guava, and grape seed extract have been used in the treatment of periodontitis. These herbs have been reported to exhibit a range of therapeutic effects, including anti-inflammatory, antiplaque, antihalitosis, antiresorptive, antioxidant, antibacterial, antifungal, antiviral, and antimicrobial properties. These components can be utilized in various forms such as mouth rinse, gel, oil, toothpaste, aqueous extract, mouthwash, or tooth powder.
CONCLUSIONS: Several readily available herbal formulations are now available on the market and have been shown to be effective as supplemental periodontal phytotherapy. However, these should be used under the supervision of a dental professional to ensure optimal benefits and effectiveness. Therefore, it is necessary to improve the understanding of suggested herbal prescription practices among dental professionals.

Using skin patches to deliver drugs is dependable and doesn\'t have the same issues as permeation enhancers, which help drugs get through the skin but struggle because of the skin\'s natural barrier. Strategies are required to increase topical bioavailability to enhance drug absorption. Natural compounds offer a promising solution by temporarily reducing skin barrier resistance and improving drug absorption. Natural substances allow a wider variety of medications to be distributed through the stratum corneum, offering a dependable approach to enhancing transdermal drug delivery. Natural substances have distinct advantages as permeability enhancers. They are pharmacologically effective and safe, inactive, non-allergenic, and non-irritating. These characteristics ensure their suitability for use without causing adverse effects. Natural compounds are readily available and well tolerated by the body. Studies investigating the structure-activity relationship of natural chemicals have demonstrated significant enhancer effects. By understanding the connection between chemical composition and enhancer activity, researchers can identify effective natural compounds for improving drug penetration. In conclusion, current research focuses on utilizing natural compounds as permeability enhancers in transdermal therapy systems. These substances offer safety, non-toxicity, pharmacological inactivity, and non-irritation. Through structure-activity relationship investigations, promising advancements have been made in enhancing drug delivery. Using natural compounds holds enormous potential for improving the penetration of trans-dermally delivered medications.

Researchers and clinicians need to be aware of procedures that are more adaptable to new and different environments in premature infants; therefore, it is important to conduct a comprehensive review of the effect of aromatherapy on apnea attacks and oxygen saturation (SpO2 ) in premature newborns. In this review, databases such as PubMed, Scopus, Web of Science, and Cochrane Library were systematically searched without language and time limitations up to November 1, 2022. Initially, 153 studies were founded, and after duplicate removal, title as well as full-text review, seven studies were enrolled in the final analysis. Studies indicated that aromatherapy with Rosa damascena, vanilla, and breast milk odors could significantly reduce apneas in preterm infants and improve SpO2 levels. Hence, aromatherapy could consider as an effective adjuvant treatment for the reduction of apnea attacks among preterm infants.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of Chinese herbal medicines (CHMs) on hematologic manifestations in patients with systemic lupus erythematosus (SLE).
METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Airiti Library were searched for the period January 2000 to February 2022.
METHODS: RCTs involving CHMs in patients with SLE with available hematologic data.
METHODS: The primary outcomes included white blood cell (WBC) count, hemoglobin level, and platelet count. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. Sensitivity analysis of RCTs with abnormal hematologic data before intervention was performed to verify the robustness of the results. Subgroup analysis was also applied for results with high heterogenicity. Core patterns of used herbal drug pairs had also been analyzed and visualized.
RESULTS: Fifteen RCTs involving 1183 participants were included. The effects of elevating WBC count (weighted mean difference [WMD]: 0.69; 95% confidence interval [CI]: 0.33-1.06; p <0.001), hemoglobin levels (WMD: 0.64; 95% CI: 0.31-0.97; p <0.001), and platelet count (WMD: 0.61; 95% CI: 0.48-0.74; p <0.001) in the CHM group were significantly greater than those in the control group. In total, 23 single herbs and 152 herbal drug pairs were identified for core patterns network analysis.
CONCLUSIONS: We demonstrated significantly superior therapeutic effects achieved with CHMs and conventional therapy regarding leukopenia, anemia, and thrombocytopenia compared to that of conventional therapy alone in patients with SLE.

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.

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.

Depression is a mental health disorder that develops as a result of complex psycho-neuro-immuno-endocrinological disturbances. This disease presents with mood disturbances, persistent sadness, loss of interest and impaired cognition, which causes distress to the patient and significantly affects the ability to function and have a satisfying family, social and professional life. Depression requires comprehensive management, including pharmacological treatment. Because pharmacotherapy of depression is a long-term process associated with the risk of numerous adverse drug effects, much attention is paid to alternative therapy methods, including phytopharmacotherapy, especially in treating mild or moderate depression. Preclinical studies and previous clinical studies confirm the antidepressant activity of active compounds in plants, such as St. John\'s wort, saffron crocus, lemon balm and lavender, or less known in European ethnopharmacology, roseroot, ginkgo, Korean ginseng, borage, brahmi, mimosa tree and magnolia bark. The active compounds in these plants exert antidepressive effects in similar mechanisms to those found in synthetic antidepressants. The description of phytopharmacodynamics includes inhibiting monoamine reuptake and monoamine oxidase activity and complex, agonistic or antagonistic effects on multiple central nervous system (CNS) receptors. Moreover, it is noteworthy that the anti-inflammatory effect is also important to the antidepressant activity of the plants mentioned above in light of the hypothesis that immunological disorders of the CNS are a significant pathogenetic factor of depression. This narrative review results from a traditional, non-systematic literature review. It briefly discusses the pathophysiology, symptomatology and treatment of depression, with a particular focus on the role of phytopharmacology in its treatment. It provides the mechanisms of action revealed in experimental studies of active ingredients isolated from herbal antidepressants and presents the results of selected clinical studies confirming their antidepressant effectiveness.