In recent years, the incidence of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, has shown a steadily rising trend, which has posed a major challenge to the global public health. Traditional Chinese Medicine (TCM), with its multi-component and multi-target characteristics, offers a promising approach for the treatment of neurodegenerative diseases. However, it is difficult to comprehensively elucidate the complex mechanisms underlying TCM formulations. As an emerging systems biology approach, network pharmacology has provided a crucial tool for uncovering the multi-target mechanisms of TCM through high-throughput technologies, molecular docking, and network analysis. This paper reviews the advancements in the application of network pharmacology in treating neurodegenerative diseases with TCM, analyzes the current status of relevant databases and technological methods, discusses the limitations in the research, and proposes future directions to promote the modernization of TCM and the development of precision medicine. Keywords: Neurodegenerative diseases, Traditional Chinese Medicine, Network pharmacology, Therapeutic targets.

Lonicera caerulea var. kamtschatica (LCK), known as blue honeysuckle or haskap berry, is rich in bioactive compounds such as polyphenols, flavonoids, and anthocyanins, which are linked to various health benefits, including anti-inflammatory and antioxidant properties. The research specifically investigates the effects of an LCK extract that has been standardized to contain a minimum of 15% anthocyanins on inflammation and oxidative stress at the cellular level. In vitro studies using A549 human lung epithelial cells and peripheral blood mononuclear cells (PBMCs) demonstrated the extract's anti-inflammatory and antioxidant properties. LCK extract significantly inhibited the nuclear translocation of NF-κB p65 and reduced the production of IL-8 in A549 cells. It also downregulated the expression of pro-inflammatory genes (RELA and PTGS2) while upregulating antioxidant genes (CAT, HMOX1, and SOD2). In PBMCs, LCK extract decreased the phosphorylation of NF-κB p65 and reduced levels of pro-inflammatory cytokines IL-1β and IL-6 following LPS stimulation. Additionally, the extract inhibited reactive oxygen species (ROS) formation and nitric oxide (NO) production, demonstrating its potential to modulate oxidative stress. Furthermore, in vitro assays indicated that LCK extract could hinder the binding of SARS-CoV-2 spike protein to the hACE2 receptor, suggesting antiviral potential. These findings suggest that LCK extract exerts significant anti-inflammatory and antioxidant effects, indicating its potential as a functional food ingredient or dietary supplement to combat inflammation and oxidative stress.

Lipophilicity and blood partitioning are important determinants for predicting toxicokinetics using physiologically-based toxicokinetic (PBTK) modeling. In this study, the logarithm of the -octanol:water partition coefficient (log) and the blood-to-plasma concentration ratio ( ) were for the first time experimentally determined for the pyrrolizidine alkaloids (PAs) intermedine, lasiocarpine, monocrotaline, retrorsine and their -oxides (PANOs). Validated assays for log (miniaturized shake-flask method) and (LC-MS/MS-based depletion assay) determination were compared to an ensemble of models. Experimentally determined log indicate a higher affinity of PAs and PANOs to the aqueous compared to the organic phase. Depending on the method, determined log overpredicted the experimental values by ≥ 1 log unit for 3 out of 4 PAs (SPARC), 4 out of 6 PAs and PANOs (CLOGP), 5 out of 8 PAs and PANOs (KowWIN) and 3 out of 8 PAs and PANOs (S+logP). obtained suggested a low binding affinity of PAs and PANOs towards red blood cells. For all 8 PAs and PANOs, predicted deviated from experimental values by less than 50%. In conclusion, for PBTK modeling of PAs and PANOs, experimental log should be preferred, while predicted by the acid/base classification model is a suitable surrogate for experimental data.

(ES) exerts various pharmacological effects, including renoprotection in a rat model of renal ischemia-reperfusion injury. However, the mechanisms of these effects remain unclear. Therefore, we investigated the effects and mechanisms of ES on aristolochic acid (AA)-induced acute kidney injury in mice. The experimental mice were divided into the control group, the model group (AA-induced acute kidney injury model), the model + ES group ( boiled-free granules treated by gavage for two weeks), the model + fasudil group (fasudil administered intraperitoneally for three days), and the model + ES + fasudil group. After AA intervention in normal mice, the expression of ASC and NLRP3 and the levels of IL-1, IL-18, and TNF- were significantly elevated in mouse renal tissues (P < 0.05). However, AA-induced renal dysfunction was ameliorated by both ES and fasudil, which was confirmed by the decrease in serum creatinine and blood urea nitrogen levels, as well as by renal histopathological abnormalities such as renal tubule dilation and tubular formation. In addition, the inflammatory response of AA-induced renal inflammation was inhibited by both ES and fasudil, and the expression of ASC and NLRP3 and the levels of IL-1, IL-18, and TNF- were significantly higher in mouse renal tissues after the treatment of either ES or fasudil (P < 0.05). ES may be a potential treatment agent for aristolochic-acid-triggered nephropathy, with inhibition of the NLRP3/IL-1 as one plausible underlying mechanism.

Oleanolic acid (OA) is a pentacyclic triterpenoid molecule widely distributed throughout medicinal plants. This naturally occurring OA has attracted considerable interest due to its wide range of pharmacological characteristics, notably its cytotoxic effects on various human cancer cell lines, making it a potential candidate for extensive therapeutic uses. In vivo studies have shown that OA possesses hepatoprotective, cardioprotective, anti-inflammatory and anti-microbial properties. The inherent obstacles of OA, such as low permeability, limited bioavailability, and poor water solubility, have restricted its therapeutic applicability. However, recent developments in drug delivery techniques have given OA an additional advantage by overcoming issues with its solubility, stability, and bioavailability. This review briefly summarises the signalling pathways involved in the pharmacological activities of OA as monotherapy and in combination with other drugs. The review devotes a substantial portion to explaining the formulation developments, emphasising nanotechnology as a key factor in the improvement of the therapeutic potential of OA. Several investigated novel formulations have been discussed, including liposomes, nanoemulsions, phospholipids, and polymeric nanoparticles, emerging synergistically as an efficient delivery of OA and several other drugs. Based on our literature evaluation, it can be inferred that the combination therapy had a more favourable outcome than using OA alone in vivo trials, primarily due to synergistic effects. However, it is essential to note that this finding was inconsistent across all investigations. The combination of OA has not yet been considered for clinical trials. However, it is interesting that neither therapy has obtained approval from the USFDA.

Alopecia is a common dermatological disorder of patchy hair loss with substantial patient burden. Phytotherapeutic compounds are increasingly used as a source of new therapeutic options. This review aimed to synthesize the evidence on plant species in hair growth and the methodological aspects of experimental models. The systematic scoping review was conducted following the PRISMA checklist, the Joanna Briggs Institute, and in accordance with Cochrane. A systematic search was carried out in the Pubmed, Scopus, Web of Science, and SciELO databases. experiments that evaluated hair growth activity using natural substances of plant origin were included. Data collection and analysis: a total of 1250 studies were identified, of which 175 were included for qualitative synthesis. Of these, 128 used mice, 37 rats, 10 rabbits, 1 guinea pig, and 1 sheep as animal models. The methodologies mapped were as follows: hair growth analysis, histological analysis, immunohistochemistry, gene expression analysis, Western blot, enzyme-linked immunosorbent assay, and biochemical analysis. Minoxidil and finasteride were the most commonly used positive controls. The studies evaluated plant species (166), algae (11), or isolated substances (31). Overall, 152 plant species and 37 isolated substances were identified. This is the first systematic scoping review on the methodological aspects of hair growth activity. We created a checklist to be completed by authors to allow data comparison and reproducibility, facilitate data interpretation by readers, and ensure better quality of evidence. This work may become a valuable tool for future research and contribute to significant advances in hair growth studies.

Chronic myeloid leukemia (CML) is a myeloproliferative disease, characterized by the presence of the oncogene BCR-ABL. Imatinib mesylate (IMA) is the first-line treatment for CML, and some treatment resistance has been reported. Natural products are rich sources of bioactive compounds with biological effects, opening a possibility to alter cell susceptibility to drugs such as imatinib. Herein, we evaluated the interference of betulinic acid and ursolic acid in glycoprotein P (P-gp) activity and the possible synergistic effect when associated with IMA by the Chou-Talalay method. Ursolic acid presented an IC of 14.0 µM and 19.6 µM for K562 and Lucena 1, respectively, whilst betulinic acid presented an IC of 8.6 µM and 12.5 µM for these cell lines. Evaluation of the combination of terpenoids and imatinib mesylate revealed that ursolic acid or betulinic acid acts in synergism with IMA, as indicated by the combination indexes (CI<1). Analysis of annexin V labeling demonstrated that a combination of IMA with betulinic acid enhances the inhibition on cell proliferation via the apoptosis pathway, with caspases 3/7 activation after 24 hours of treatment and inhibition of the STAT5/survivin pathway, decreasing cell viability. The combination of natural products and IMA on a multidrug-resistant leukemia cell line is a promising strategy for CML treatment.

Herbal decoctions always contain numerous plant microRNAs (miRNAs), and some of these can be absorbed orally to exert cross-kingdom gene regulation. However, little is known about which specific types of herbal decoction-borne plant miRNAs are more likely to be absorbed. Thus, two antiviral herbal decoctions, Qingfei Paidu (QFPD) and Qingre Huashi Kangdu (QRHS), were administered to human volunteers and rats, respectively, to investigate the characteristics of orally absorbed decoction-borne plant miRNAs. MIR-6240-3p was identified as an absorbed plant miRNA in humans and is most highly expressed in QFPD decoction. Therefore, the kinetics of MIR-6240-3p were monitored in humans following the administration of the QFPD decoction, and its antiviral effect on human coronavirus type 229E (HCoV-229E) was examined in vitro. 586,176 small RNAs (sRNAs) were identified in QFPD decoction, of which 100,276 were orally absorbed by humans. In the QRHS decoction, 124,026 sRNAs were detected, with 7484 being orally absorbed by rats. Logistical repression analysis revealed that absorbable plant sRNAs in both humans and rats presented higher expression levels, greater minimum free energy, and increased AU/UA frequencies compared to non-absorbable plant sRNAs. The amount of MIR-6240-3p in humans increased between 1- and 3-hours after the administration of the QFPD decoction. In addition, MIR-6240-3p significantly reduced the RNA copy number and TCID50 of HCoV-229E in vitro. These results suggest that herbal decoction-borne plant sRNAs with higher expression level, greater minimum free energy or an increased AU/UA frequency are more likely to be orally absorbed and could potentially mediate cross-kingdom gene regulation.

is a widespread genus comprising approximately 3500 species, both annual and perennial, found across Asia, Europe, Africa, and the Americas. In Turkey, it is represented by 63 sections and 485 taxa with a high endemism ratio (51%). In traditional medicine, the roots of various species represent very old and well-known drugs used for antiperspirant, diuretic, and tonic purposes, as well as for the treatment of nephritis, diabetes, leukemia, and uterine cancer. The genus is the richest source of cycloartane-type compounds, which display a diverse range of bioactivities, such as wound healing, immunomodulatory, antitumor, hepatoprotective, antimutagenic, antiviral, and antiprotozoal activities. Moreover, cycloastragenol, the main sapogenol of many cycloartane-type glycosides found in the genus, has gained attention as a potent telomerase activator over the past decade. The preparation of cycloastragenol derivatives could be significant in the near future due to their unique bioactivity. This review covers the botanical aspects of L., as well as the phytochemical and biological activity studies conducted on Turkish species, with a special focus on cycloartenols. It contains 36 articles reporting the phytochemistry of 29 species and 111 new compounds, including 104 triterpene saponins. In addition to the phytochemical studies, this review summarizes the biotransformation studies on cycloartanes via endophytic fungi isolated from the tissues of species.

Drynariae Rhizoma has been commonly used as a preventive and therapeutic agent for bone diseases. However, its pharmacological mechanisms have not been fully elucidated. Here, we aimed to investigate the effects of Drynariae Rhizoma in a bilateral ovariectomized rat model and explore the correlation with gut microbiome. We established an ovariectomized rat model, which we treated with different doses of Drynariae Rhizoma (Drynariae Rhizoma-Low, 0.27 g/kg/day; Drynariae Rhizoma-Middle, 0.81 g/kg/day; Drynariae Rhizoma-High, 2.43 g/kg/day) through intragastric administration for 12 weeks. Results showed that Drynariae Rhizoma alleviated body weight, moderated bone microstructure, and promoted the expression of bone formation-related factors in ovariectomized rats, in which Drynariae Rhizoma-High showed the most significant effects among the three doses. Furthermore, the effects of Drynariae Rhizoma on promoting bone formation were correlated to the changes in microbial richness and the restorations of several genera, among which and were positively correlated with the bone formation-related factors, and both were enriched in the Drynariae Rhizoma-High group as biomarkers. Moreover, CMP-legionaminate biosynthesis I might be a crucial pathway of Drynariae Rhizoma to regulate gut microbiota. The content of serum short-chain fatty acids in the ovariectomized rats were regulated by Drynariae Rhizoma. Our results demonstrate that Drynariae Rhizoma promotes bone formation in ovariectomized rats, and is related to the regulation of the gut microbiota structure.

The phytochemical study of apolar and medium polarity stem bark and leaf extracts afforded 29 compounds, including three new sesquiterpenes (1 - 3: ) and one new -ionone glycoside (4: ). All compounds were characterized by means of 1D and 2D NMR and HRESIMS data. Furthermore, a precise structural analysis was performed, employing a combined density functional theory (DFT)/NMR approach to elucidate the compounds configurations. The crude extracts were then tested against a panel of gram-positive and gram-negative bacteria by broth dilution methods to determine their minimal inhibitory concentration. In these experimental conditions, no interesting antimicrobial activity was observed.

is commonly used as traditional medicine for cutaneous wound healing. Nonetheless, the wound healing mechanisms of remain unclear. This review aims to provide insight into the molecular mechanisms of in promoting cutaneous wound healing, with particular emphasis on the mechanisms that stimulate cell proliferation and migration. has been shown to upregulate growth factors such as keratinocyte growth factor-1 (KGF-1), transforming growth factor- (TGF-), cyclin D1, insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and microfibril-associated glycoprotein 4 (MFAP4), as well as collagen, fibrillin, elastin, -smooth muscle actin (-SMA), integrins, and platelet endothelial cell adhesion molecule 1 (PECAM-1, also known as CD31), while downregulating the expression of matrix metalloproteinases (MMPs). In addition, was also found to upregulate PI3K/Akt and MAPK pathways, as well as the TGF- signalling pathway via Smad proteins. Furthermore, molecular docking studies revealed that certain chemical constituents of bind to some of the forementioned growth factors or signalling molecules. With regards to current applications, although human clinical trials have reported positive results from using in healing open wounds and burns and alleviating some inflammatory skin diseases, the current commercial uses of remain largely focused on cosmetic products. Thus, greater advances are required to promote the use of products in clinical settings.

, a significant forage plant cultivated in arid regions of northwest China, remains underexplored for its triterpenoid saponins and medicinal properties compared to the extensively studied . To explore the phytochemical profile of for its potential application in the medical field, we employed ultra-pressure liquid chromatography coupled with a tandem mass spectrometry-based method to identify cycloartane-type triterpenes. Eventually, five new cycloartane-type triterpenoids, adsurgosides A - D ( 1 - 4: ) and 3-methyl-3,4-seco-cyclostellanol (5: ), together with two known analogs, cycloastragenol (6: ) and cyclopycanthogenin (7: ), were isolated from the roots of . Their structures were elucidated using 1D and 2D NMR analyses in combination with HRESIMS data. Additionally, a comparative study on the distribution patterns of these compounds revealed qualitative and quantitative variations between and . Our findings not only identified an alternative plant for isolating cycloartane-type triterpenoids but also offer new insights into the chemical properties of .

An approach combining enzymatic inhibition and untargeted metabolomics through molecular networking was employed to search for human recombinant full-length protein tyrosine phosphatase 1B (PTP1 B) inhibitors from a collection of 66 mangrove-associated fungal taxa. This strategy prioritized two strains (IQ-1612, section , and IQ-1620, section ) for further studies. Chemical investigation of strain IQ-1612 resulted in the isolation of a new nonanolide derivative, roseoglobuloside A (1: ), along with two known metabolites (2: and 3: ), whereas strain IQ-1620 led to the isolation of four known naphtho-γ-pyrones and one known diketopiperazine (4: -8: ). Of all isolates, compounds 2, 3: , and 7: showed a marked inhibitory effect on PTP1B with an IC value < 20 µM, while 6: showed moderate inhibition with IC of 65 µM. Compounds 1: and 8: were inactive at a concentration of 100 µM, whereas 4: and 5: demonstrated significant inhibition at 20 µM. The structure of 1: was established by comprehensive spectroscopic analysis, and its relative and absolute configuration was assigned based on NOE correlations and by comparison of calculated and experimental ECD curves. Molecular docking indicated that these molecules primarily bind to two different allosteric sites, thereby inducing conformational changes that impact enzymatic activity.

Significant health and socio-economic challenges are posed by renal diseases, leading to millions of deaths annually. The costs associated with treating and caring for patients with renal diseases are considerable. Current therapies rely on synthetic drugs that often come with side effects. However, phytoestrogens, natural compounds, are emerging as promising renal protective agents. They offer a relatively safe, effective, and cost-efficient alternative to existing therapies. Phytoestrogens, being structurally similar to 17--estradiol, bind to estrogen receptors and produce both beneficial and, in some cases, harmful health effects. The activation of sirtuins has shown promise in mitigating fibrosis and inflammation in renal tissues. Specifically, SIRT1, which is a crucial regulator of metabolic activities, plays a role in protecting against nephrotoxicity, reducing albuminuria, safeguarding podocytes, and lowering reactive oxygen species in diabetic glomerular injury. Numerous studies have highlighted the ability of phytoestrogens to activate sirtuins, strengthen antioxidant defense, and promote mitochondrial biogenesis, playing a vital role in renal protection during kidney injury. These findings support further investigation into the potential role of phytoestrogens in renal protection. This manuscript reviews the potential of phytoestrogens such as resveratrol, genistein, coumestrol, daidzein, and formononetin in regulating sirtuin activity, particularly SIRT1, and thereby providing renal protection. Understanding these mechanisms is crucial for designing effective treatment strategies using naturally occurring phytochemicals against renal diseases.

Podophyllotoxin is derived from plant sources and exhibits strong anticancer activity. However, limited natural availability and environmental impacts from traditional extraction methods drive the search for alternative production approaches. This review explores diverse strategies for sustainable podophyllotoxin synthesis, including biosynthesis, semi-synthesis, and biotransformation. Biosynthetic methods involve metabolic pathway engineering in plant or microbial cells, enabling increased yields by manipulating precursor availability and gene expression. Semi-synthetic approaches modify podophyllotoxin precursors or intermediates to enhance therapeutic effects, with derivatives like etoposide and teniposide showing clinical efficacy. Biotransformation, utilising organisms such as endophytic fungi or human hepatic enzymes, enables the transformation of substrates like deoxypodophyllotoxin into podophyllotoxin or its derivatives, yielding compounds with reduced environmental impact and improved purity. The anticancer efficacy of podophyllotoxin and its derivatives stems from multiple mechanisms. These compounds disrupt cell mitosis by inhibiting microtubule assembly, impairing nucleoside transport, and blocking topoisomerase II activity, leading to DNA cleavage and cancer cell apoptosis. Podophyllotoxin and its derivatives also exhibit anti-angiogenesis and anti-metastatic effects through signalling pathway modulation. Notably, derivatives like deoxypodophyllotoxin utilise advanced delivery systems, enhancing targeted efficacy and reducing side effects. Given the varied mechanisms and growing therapeutic applications, optimising biotransformation and delivery techniques remains essential for advancing podophyllotoxin-based therapies. This comprehensive review underscores the compound's potential as a robust anticancer agent and the need for continued research to maximise its production and clinical effectiveness.

has been traditionally used to strengthen the immune system. Therefore, herein, we investigated the potential of aqueous extracts (AEs) obtained from flowers (F), leaves (L), or roots (R) as an immune booster in human primary monocyte-derived macrophages (hMDMs). Additionally, to identify the main class of compounds (phenolic/carboxylic acids vs. alkylamides) responsible for the bioactivity, the three AEs were fractioned by semi-preparative high-performance liquid chromatography (HPLC). The AEs and the isolated phenolic/carboxylic acidic fractions were not cytotoxic for hMDMs for all tested concentrations, as confirmed by the metabolic activity and DNA content assays. Moreover, AE drastically induced the production of the interleukin (IL)-6 and tumor necrosis factor (TNF)-, with a minimal effect on IL-1 and prostaglandin E2 (PGE2), supporting their potential for macrophage activation. Interestingly, in the presence of the phenolic/carboxylic acidic fractions, this efficacy considerably decreased, suggesting a complementary effect between compounds. AE also triggered the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2 and p38 signaling pathways and upregulated the cyclooxygenase (COX)-2 expression in hMDMs. Overall, AE-F was demonstrated to be the most powerful immunostimulant extract that can be related to their higher number in identified bioactive compounds compared to AE-L and AE-R. These results highlight the efficiency of AE to enhance the function of a key cell type of the immune system and their potential as immunostimulant formulations for patients with a compromised immune system due to certain diseases (e.g., acquired immunodeficiencies) and treatments (e.g., chemotherapy).

Infections with virus can cause severe ocular diseases and encephalitis. The present study aimed to investigate potential inhibitors of fusion between HSV-1 and the cellular membrane of the host cell. Fusion and entry of HSV-1 into the host cell is mimicked by a virus-free eukaryotic cell culture system by co-expression of the HSV-1 glycoproteins gD, gH, gL, and gB in presence of a gD receptor, resulting in excessive membrane fusion and polykaryocyte formation. A microscopic read-out was used for the screening of potential inhibitors, whereas luminometric quantification of cell-cell fusion was used in a reporter fusion assay. HSV-1 gB was tagged at its C-terminus with mCherry to express mCherry-gB in both assay systems for the visualization of the polykaryocyte formation. Reporter protein expression of SEAP was regulated by a Tet-On 3 G system. The saponin mixture aescin was identified as the specific inhibitor (IC 7.4 µM, CC 24.3 µM, SI 3.3) of membrane fusion. A plaque reduction assay on Vero cells reduced HSV-1 entry into cells and HSV-1 cell-to-cell spread significantly; 15 µM aescin decreased relative plaque counts to 41%, and 10 µM aescin resulted in a residual plaque size of 11% (HSV-1 17 syn) and 2% (HSV-1 ANG path). Release of the HSV-1 progeny virus was reduced by one log step in the presence of 15 µM aescin. Virus particle integrity was mainly unaffected. Analytical investigation of aescin by UHPLC-MS revealed aescin IA and -IB and isoaescin IA and -IB as the main compounds with different functional activities. Aescin IA had the lowest IC, the highest CC, and an SI of > 4.6.

This exploratory study was designed to identify factors implicating microbial influence on medicinal plant metabolomes. Utilizing a whole-microbiome approach, amplicon sequencing was used to identify the makeup of fungal and bacterial assemblages from endophytic (interior) and epiphytic (external) environments in two different sets of congeneric host-plant pairs, with collection of multiple samples of two medicinal plant species () and two generic analogs (). Diversity analysis of microbial assemblages revealed the influence of three primary factors driving variance in microbial community composition: host-plant taxonomy, the compartmentalization of microbial communities within discrete plant parts, and the scale of distance (microhabitat heterogeneity) between sampling locations. These three factors accounted for ~ 60% of variance within and between investigated microbiomes. Across all our collections, bacterial populations were more diverse than fungi (per compartment), and microbial density in epiphytic compartments (aerial parts, rhizosphere) were higher than those of endophytes (leaf and root). These comparative data point to key loci associated with variation between congeneric pairs and plant genera, providing insight into the complex and contrasting relationships found within this multi-kingdom coevolutionary relationship. Although reflective of only a limited set of botanical source materials, these data document the richness of a relatively unexplored component of the plant world and highlight the relevance of a whole-microbiome ecology-driven approach to botanical research and directed natural product investigations.

Painful diabetic neuropathy (PDN) is a highly prevalent complication in patients suffering from diabetes mellitus. Given the inadequate pain-relieving effect of current therapies for PDN, there is a high unmet medical need for specialized therapeutic options. In traditional Chinese medicine (TCM), various herbal formulations have been implemented for centuries to relieve pain, and one commonly used plant in this context is (). Here, we summarize the chemical constituents of including their pharmacological mechanisms-of-action and discuss potential benefits for the treatment of PDN. For this, data, as well as preclinical and clinical studies, were critically reviewed and comprehensively compiled. Our findings reveal that and its individual constituents exhibit a variety of pharmacological properties relevant for PDN, including antinociceptive, anti-inflammatory, antioxidant, and antiapoptotic activities. Through this multifaceted and complex combination of various pharmacological effects, relevant hallmarks of PDN are specifically addressed, suggesting that may represent a promising source for novel therapeutic approaches for PDN.

Curcumin is the main ingredient of the Chinese herbal turmeric rhizome, used to treat tumors, diabetes, inflammation, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, and liver diseases. The antitumor effects of curcumin have received even more attention. One of the main mechanisms of antitumor effects includes inhibition of tumor invasion and migration, induction of tumor cell apoptosis, and inhibition of various cell signaling pathways. It has been found that the antitumor biological activity of curcumin in the body is associated with epigenetic mechanisms. That also implies that curcumin may act as a potential epigenetic modulator to influence the development of tumor diseases. The immune system plays an essential role in the development of tumorigenesis. Tumor immunotherapy is currently one of the most promising research directions in the field of tumor therapy. Curcumin has been found to have significant regulatory effects on tumor immunity and is expected to be a novel adjuvant for tumor immunity. This paper summarizes the antitumor effects of curcumin from four aspects: molecular and epigenetic mechanisms of curcumin against a tumor, mechanisms of curcumin modulation of tumor immunotherapy, reversal of chemotherapy resistance, and novel drug delivery system of curcumin, which provide new directions for the development of new antitumor drugs.