Therapeutic Effects of Natural Products on Human Diseases

Evodiamine is an alkaloid found in Evodia fruits, a traditional Chinese medicine. Preclinical studies have demonstrated its anti-inflammatory and neuroprotective properties. The 2,4-dinitro-1-chloro-benzene (DNCB) was used to test the effects of evodiamine on a chemically induced atopic dermatitis-like model in BALB/c mice. Evodiamine significantly lowered serum immunoglobulin E levels, which increased as an immune response to the long-term application of DNCB. Several atopic dermatitis-like skin symptoms induced by DNCB, including skin thickening and mast cell accumulation, were suppressed by evodiamine therapy. DNCB induced higher levels of pro-inflammatory cytokines in type 2 helper T (Th2) cells (IL-4 and IL-13), Th1 cells (IFN-γ and IL-12A), Th17 cells (IL-17A), Th22 cells (IL-22), and chemokines (IL-6 and IL-8). These increases were suppressed in the lymph nodes and skin following evodiamine treatment. The results of our study indicate that evodiamine suppresses atopic dermatitis-like responses in mice and may therefore be useful in treating these conditions. Full article

In traditional Korean medicines, Magnolia officinalis is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of Magnolia officinalis. Its pharmacological effects include anti-inflammatory, hepatoprotective, and antioxidant effects. Using BALB/c mice repeatedly exposed to 1-chloro-2,4-dinitrobenzene (DNCB), magnolol was evaluated in atopic dermatitis-like lesions. Administration of magnolol (10 mg/kg, intraperitoneal injection) markedly relieved the skin lesion severity including cracking, edema, erythema, and excoriation, and significantly inhibited the increase in IgE levels in the peripheral blood. A DNCB-induced increase in mast cell accumulation in atopic dermatitis skin lesions was reversed by magnolol administration, as well as a rise in expression levels of pro-inflammatory Th2/Th17/Th1 cytokines’ (IL-4, IL-13, IL-17A, IFN-γ, IL-12A, TARC, IL-8, and IL-6) mRNAs in the lymph nodes and skin (n = 5 per group). In lymph nodes, magnolol reversed DNCB’s increase in CD4⁺RORγt⁺ Th17 cell fraction and decrease in CD4⁺FoxP3⁺ regulatory T cell fraction. The results also showed that magnolol suppressed T cell differentiation into Th17 and Th2 cells, but not Th1 cells. Magnolol suppresses atopic dermatitis-like responses in the lymph nodes and skin, suggesting that it may be feasible to use it as a treatment for atopic dermatitis through its suppression of Th2/Th17 differentiation. Full article

Background: Lung cancer is the predominant cause of cancer-related fatalities. This prompted our exploration into the anti-lung cancer efficacy of Labisia pumila, a species meticulously selected from the preliminary screening of 600 plants. Methods: Through the strategic implementation of activity-guided fractionation, ardisiacrispin A (1) was isolated utilizing sequential column chromatography. Structural characterization was achieved employing various spectroscopic methods, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR). Results: L. pumila 70% EtOH extract showed significant toxicity in A549 lung cancer cells, with an IC₅₀ value of 57.04 ± 10.28 µg/mL, as well as decreased expression of oncogenes and induced apoptosis. Compound 1, ardisiacrispin A, induced a 50% cell death response in A549 cells at a concentration of 11.94 ± 1.14 µg/mL. Conclusions: The present study successfully investigated ardisiacrispin A extracted from L. pumila leaves, employing a comprehensive spectroscopic approach encompassing NMR, IR, and MS analyses. The anti-lung cancer efficacy of ardisiacrispin A and L. pumila extract was successfully demonstrated for the first time, to the best of our knowledge. Full article

According to the available ethnobotanical data, the Bouvardia ternifolia plant has long been used in Mexican traditional medicine to relieve the symptoms of inflammation. In the present study, the cytotoxic effect of extracts obtained from the flowers, leaves and stems of B. ternifolia using hexane, ethyl acetate (AcOEt) and methanol (MeOH) was evaluated by applying them to the SiHa and MDA-MB-231 cancer cell lines. An MTT reduction assay was carried out along with = biological activity assessments, and the content of total phenols, tannins, anthocyanins, betalains and saponins was quantified. According to the obtained results, nine extracts exhibited a cytotoxic effect against both the SiHa and MDA lines. The highest cytotoxicity was measured for leaves treated with the AcOEt (ID₅₀ of 75 µg/mL was obtained for MDA and 58.75 µg/mL for SiHa) as well as inhibition on ABTS•⁺ against DPPH• radical, while MeOH treatment of stems and AcOEt of flowers yielded the most significant antioxidant capacity (90.29% and 90.11% ABTS•⁺ radical trapping). Moreover, the highest phenolic compound content was measured in the stems (134.971 ± 0.294 mg EAG/g), while tannins were more abundant in the leaves (257.646 mg eq cat/g) and saponins were most prevalent in the flowers (20 ± 0 HU/mg). Screening tests indicated the presence of flavonoids, steroids, terpenes and coumarins, as well as ursolic acid, in all the studied extracts. These results demonstrate the biological potential of B. ternifolia. Full article

Cardiac hypertrophy is developed by various diseases such as myocardial infarction, valve diseases, hypertension, and aortic stenosis. Sibjotang (十棗湯, Shizaotang, SJT), a classic formula in Korean traditional medicine, has been shown to modulate the equilibrium of body fluids and blood pressure. This research study sought to explore the impact and underlying process of Sibjotang on cardiotoxicity induced by DOX in H9c2 cells. In vitro, H9c2 cells were induced by DOX (1 μM) in the presence or absence of SJT (1–5 μg/mL) and incubated for 24 h. In vivo, SJT was administrated to isoproterenol (ISO)-induced cardiac hypertrophy mice (n = 8) at 100 mg/kg/day concentrations. Immunofluorescence staining revealed that SJT mitigated the enlargement of H9c2 cells caused by DOX in a dose-dependent way. Using SJT as a pretreatment notably suppressed the rise in cardiac hypertrophic marker levels induced by DOX. SJT inhibited the DOX-induced ERK1/2 and p38 MAPK signaling pathways. In addition, SJT significantly decreased the expression of the hypertrophy-associated transcription factor GATA binding factor 4 (GATA 4) induced by DOX. SJT also decreased hypertrophy-associated calcineurin and NFAT protein levels. Pretreatment with SJT significantly attenuated DOX-induced apoptosis-associated proteins such as Bax, caspase-3, and caspase-9 without affecting cell viability. In addition, the results of the in vivo study indicated that SJT significantly reduced the left ventricle/body weight ratio level. Administration of SJT reduced the expression of hypertrophy markers, such as ANP and BNP. These results suggest that SJT attenuates cardiac hypertrophy and heart failure induced by DOX or ISO through the inhibition of the calcineurin/NFAT/GATA4 pathway. Therefore, SJT may be a potential treatment for the prevention and treatment of cardiac hypertrophy that leads to heart failure. Full article

Paclitaxel-induced neuropathic pain (PINP) is a serious adverse effect of chemotherapy. Dendrobii caulis (D. caulis) is a new food source used as herbal medicine in east Asia. We examined the antinociceptive effects of D. caulis extract on PINP and clarified the mechanism of action of transient receptor potential vanilloid 1 receptor (TRPV1) in the spinal cord. PINP was induced in male mice using multiple intraperitoneal injections of paclitaxel (total dose, 8 mg/kg). PINP was maintained from D10 to D21 when assessed for cold and mechanical allodynia. Oral administration of 300 and 500 mg/kg D. caulis relieved cold and mechanical allodynia. In addition, TRPV1 in the paclitaxel group showed increased gene and protein expression, whereas the D. caulis 300 and 500 mg/kg groups showed a significant decrease. Among various substances in D. caulis, vicenin-2 was quantified by high-performance liquid chromatography, and its administration (10 mg/kg, i.p.) showed antinociceptive effects similar to those of D. caulis 500 mg/kg. Administration of the TRPV1 antagonist capsazepine also showed antinociceptive effects similar to those of D. caulis, and D. caulis is thought to exhibit antinociceptive effects on PINP by modulating the spinal TRPV1. Full article

Androgenic alopecia (AGA) is a dermatological disease with psychosocial consequences for those who experience hair loss. AGA is linked to an increase in androgen levels caused by an excess of dihydrotestosterone in blood capillaries produced from testosterone by 5α-reductase type II (5αR2), which is expressed in scalp hair follicles; 5αR2 activity and dihydrotestosterone levels are elevated in balding scalps. The diverse health benefits of flavonoids have been widely reported in epidemiological studies, and research interest continues to increase. In this study, a virtual screening approach was used to identify compounds that interact with active site residues of 5αR2 by screening a library containing 241 flavonoid compounds. Here, we report two potent flavonoid compounds, eriocitrin and silymarin, that interacted strongly with 5αR2, with binding energies of −12.1 and −11.7 kcal/mol, respectively, which were more significant than those of the control, finasteride (−11.2 kcal/mol). Molecular dynamic simulations (200 ns) were used to optimize the interactions between compounds and 5αR2 and revealed that the interaction of eriocitrin and silymarin with 5αR2 was stable. The study shows that eriocitrin and silymarin provide developmental bases for novel 5αR2 inhibitors for the management of AGA. Full article

Lawsonia inermis, known as henna, has traditionally been utilized in cosmetics and folk medicine because of their valuable health effects. A lack of information about the processes that increase or decrease release, as well as the biological activities of constituents of natural origin, is an important pharmacological problem. This investigation evaluates the influence of moist heat on the flavonoid and phenolic contents of henna powder and their biological activities. HPLC analysis reflected the existence of 20 and 19 compounds of flavonoids and phenolics in the extract of unpre-treated henna by moist heat (UPMH) and pre-treated henna by moist heat (PMH). Several compounds such as chlorogenic acid, ellagic acid, rutin, rosmarinic acid, kaempferol, and pyrocatechol occurred with high concentrations of 57,017.33, 25,821.09, 15,059.88, 6345.08, 1248.42, and 819.19 µg/mL UPMH while occurred with low concentrations of 44,286.51, 17,914.26, 3809.85, 5760.05, 49.01, and 0.0 µg/mL, respectively in PMH. C. albicans, C. tropicalis, and G. candidum were more affected by UPMH with inhibition zones of 30.17 ± 0.29, 27 ± 0.5, and 29 ± 1.5 mm than PMH with inhibition zones of 29 ± 0.5, 25.33 ± 0.58, and 24.17 ± 0.29 mm, respectively. UPMH henna exhibited less MIC and MFC against the tested yeasts than PMH. Moreover, UPMH henna showed good wound healing, where the rat of migration, wound closure %, and area difference % were 14.806 um, 74.938 um², and 710.667% compared with PMH henna 11.360 um, 59.083 um², 545.333%, respectively. Antioxidant activity of UPMH and PMH henna. Promising antioxidant activity was recorded for both UPMH or PMH henna with IC₅₀ 5.46 µg/mL and 7.46 µg/mL, respectively. The docking interaction of chlorogenic acid and ellagic acid with the crystal structures of G. candidum (4ZZT) and C. albicans (4YDE) was examined. The biological screening demonstrated that the compounds had favorable docking results with particular proteins. Chlorogenic acid had robust behavior in the G. candidum (4ZZT) active pocket and displayed a docking score of −7.84379 Kcal/mol, higher than ellagic acid’s −6.18615 Kcal/mol. Full article

Propolis is a natural mixture of resins, wax, and pollen from plant buds and flowers, enriched with enzymes and bee saliva. It also contains various essential oils, vitamins, mineral salts, trace elements, hormones, and ferments. It has been found that propolis possesses antimicrobial, antiviral, and anti-inflammatory properties. We have studied the antiviral activity of six extracts of Bulgarian propolis collected from six districts of Bulgaria. The study was conducted against structurally different viruses: human coronavirus strain OC-43 (HCoV OC-43) and human respiratory syncytial virus type 2 (HRSV-2) (enveloped RNA viruses), human herpes simplex virus type 1 (HSV-1) (enveloped DNA virus), human rhinovirus type 14 (HRV-14) (non-enveloped RNA virus) and human adenovirus type 5 (HadV-5) (non-enveloped DNA virus). The influence of the extracts on the internal replicative cycle of viruses was determined using the cytopathic effect (CPE) inhibition test. The virucidal activity, its impact on the stage of viral adsorption to the host cell, and its protective effect on healthy cells were evaluated using the final dilution method, making them the focal points of interest. The change in viral infectivity under the action of propolis extracts was compared with untreated controls, and Δlgs were determined. Most propolis samples administered during the viral replicative cycle demonstrated the strongest activity against HCoV OC-43 replication. The influence of propolis extracts on the viability of extracellular virions was expressed to a different degree in the various viruses studied, and the effect was significantly stronger in those with an envelope. Almost all extracts significantly inhibited the adsorption step of the herpes virus and, to a less extent, of the coronavirus to the host cell, and some of them applied before viral infection demonstrated a protective effect on healthy cells. Our results enlarge the knowledge about the action of propolis and could open new perspectives for its application in viral infection treatment. Full article

It is worth noting that laurel (Laurus nobilis L.) contains several pharmacologically and nutritionally active compounds that may differ according to the pretreatment process. The current study is designed to clarify the effect of moist heat on the phenolic and flavonoid constituents and anti-Helicobacter pylori, antioxidant, antidiabetic, and anti-Alzheimer’s activities of laurel leaf extract (LLE). Unmoist-heated (UMH) and moist-heated (MH) LLEs showed the presence of numerous flavonoid and phenolic constituents, although at different levels of concentration. MH significantly induced (p < 0.05) the occurrence of most compounds at high concentrations of 5655.89 µg/mL, 3967.65 µg/mL, 224.80 µg/mL, 887.83 µg/mL, 2979.14 µg/mL, 203.02 µg/mL, 284.65 µg/mL, 1893.66 µg/mL, and 187.88 µg/mL, unlike the detection at low concentrations of 3461.19 µg/mL, 196.96 µg/mL, 664.12 µg/mL, 2835.09 µg/mL, 153.26 µg/mL, 254.43 µg/mL, 1605.00 µg/mL, 4486.02 µg/mL, and 195.60 µg/mL using UMH, for naringenin, methyl gallate, caffeic acid, rutin, ellagic acid, coumaric acid, vanillin, ferulic acid, and hesperetin, respectively. Chlorogenic acid, syringic acid, and daidzein were detected in the UMH LLE but not in the MH LLE, unlike pyrocatechol. The anti-H. pylori activity of the UMH LLE was lower (23.67 ± 0.58 mm of inhibition zone) than that of the MH LLE (26.00 ± 0.0 mm of inhibition zone). Moreover, the values of MIC and MBC associated with the MH LLE were very low compared to those of the UMH LLE. Via MBC/MIC index calculation, the UMH and MH LLEs showed cidal activity. The MH LLE exhibited higher anti-biofilm activity (93.73%) compared to the anti-biofilm activity (87.75%) of the MH LLE against H. pylori. The urease inhibition percentage was more affected in the UMH LLE compared to the MH LLE, with significant (p < 0.05) IC₅₀ values of 34.17 µg/mL and 91.11 µg/mL, respectively. Promising antioxidant activity was documented with a very low value of IC₅₀ (3.45 µg/mL) for the MH LLE compared to the IC₅₀ value of 4.69 µg/mL for the UMH LLE and the IC₅₀ value of 4.43 µg/mL for ascorbic acid. The MH LLE showed significantly higher (p < 0.05) inhibition of α-glucosidase and butyrylcholinesterase activities, with IC₅₀ values of 9.9 µg/mL and 17.3 µg/mL, respectively, compared to those of the UMH LLE at 18.36 µg/mL and 28.92 µg/mL. The molecular docking of naringenin showed good docking scores against acetylcholinesterase 1E66 and butyrylcholinesterase 6EMI, indicating that naringenin is an intriguing candidate for additional research as a possible medication for Alzheimer’s disease. Full article

Policosanol consumption has been associated with treating blood pressure and dyslipidemia by increasing the level of high-density lipoproteins-cholesterol (HDL-C) and HDL functionality. Although policosanol supplementation also ameliorated liver function in animal models, it has not been reported in a human clinical study, particularly with a 20 mg doage of policosanol. In the current study, twelve-week consumption of Cuban policosanol (Raydel^®) significantly enhanced the hepatic functions, showing remarkable decreases in hepatic enzymes, blood urea nitrogen, and glycated hemoglobin. From the human trial with Japanese participants, the policosanol group (n = 26, male 13/female 13) showed a remarkable decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline up to 21% (p = 0.041) and 8.7% (p = 0.017), respectively. In contrast, the placebo group (n = 26, male 13/female 13) showed almost no change or slight elevation. The policosanol group showed a 16% decrease in γ-glutamyl transferase (γ-GTP) at week 12 from the baseline (p = 0.015), while the placebo group showed a 1.2% increase. The policosanol group exhibited significantly lower serum alkaline phosphatase (ALP) levels at week 8 (p = 0.012), week 12 (p = 0.012), and after 4-weeks (p = 0.006) compared to those of the placebo group. After 12 weeks of policosanol consumption, the ferric ion reduction ability and paraoxonase of serum were elevated by 37% (p < 0.001) and 29% (p = 0.004) higher than week 0, while placebo consumption showed no notable changes. Interestingly, glycated hemoglobin (HbA_1c) in serum was lowered significantly in the policosanol group 4 weeks after consumption, which was approximately 2.1% (p = 0.004) lower than the placebo group. In addition, blood urea nitrogen (BUN) and uric acid levels were significantly lower in the policosanol group after 4 weeks: 14% lower (p = 0.002) and 4% lower (p = 0.048) than those of the placebo group, respectively. Repeated measures of ANOVA showed that the policosanol group had remarkable decreases in AST (p = 0.041), ALT (p = 0.008), γ-GTP (p = 0.016), ALP (p = 0.003), HbA_1c (p = 0.010), BUN (p = 0.030), and SBP (p = 0.011) from the changes in the placebo group in point of time and group interaction. In conclusion, 12 weeks of 20 mg consumption of policosanol significantly enhanced hepatic protection by lowering the serum AST, ALT, ALP, and γ-GTP via a decrease in glycated hemoglobin, uric acid, and BUN with an elevation of serum antioxidant abilities. These results suggest that improvements in blood pressure by consumption of 20 mg of policosanol (Raydel^®) were accompanied by protection of liver function and enhanced kidney function. Full article

Neuroinflammation is the major cause of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Currently available drugs present relatively low efficacy and are not capable of modifying the course of the disease or delaying its progression. Identifying well-tolerated and brain-penetrant agents of plant origin could fulfil the pressing need for novel treatment techniques for neuroinflammation. Attention has been drawn to a large family of flavonoids in citrus fruits, which may function as strong nutraceuticals in slowing down the development and progression of neuroinflammation. This review is aimed at elucidating and summarizing the effects of the flavonoid tangeretin (TAN) in the management of neuroinflammation-mediated neurodegenerative disorders. A literature survey was performed using various resources, including ScienceDirect, PubMed, Google Scholar, Springer, and Web of Science. The data revealed that TAN exhibited immense neuroprotective effects in addition to its anti-oxidant, anti-diabetic, and peroxisome proliferator-activated receptor-γ agonistic effects. The effects of TAN are mainly mediated through the inhibition of oxidative and inflammatory pathways via regulating multiple signaling pathways, including c-Jun N-terminal kinase, phosphoinositide 3-kinase, mitogen-activated protein kinase, nuclear factor erythroid-2-related factor 2, extracellular-signal-regulated kinase, and CRE-dependent transcription. In conclusion, the citrus flavonoid TAN has the potential to prevent neuronal death mediated by neuroinflammatory pathways and can be developed as an auxiliary therapeutic agent in the management of neurodegenerative disorders. Full article

Bowiea volubilis subsp. volubilis is primarily used to address human respiratory infections, coughs, and colds due to its diverse pharmaceutical properties. Notably, the plant contains alkaloids that exhibit notable antifungal, antibacterial, and cytotoxic properties. Additionally, the presence of saponins, with recognized antioxidant and anticancer attributes, further contributes to its medicinal potential. Steroid compounds inherent to the plant have been associated with anti-inflammatory and anticancer activities. Moreover, the bulb of B. volubilis has been associated as a source of various cardiac glycosides. Despite these therapeutic prospects, B. volubilis remains inedible due to the presence of naturally occurring toxic substances that pose risks to both animals and humans. The review focuses on a comprehensive exploration concerning B. volubilis ethnobotanical applications, phytochemical properties, and diverse biological activities in relation to in vitro and in vivo applications for promoting human health and disease prevention. The aim of the study is to comprehensively investigate the phytochemical composition, bioactive compounds, and potential medicinal properties of Bowiea volubilis, with the ultimate goal of uncovering its therapeutic applications for human health. This review also highlights an evident gap in research, i.e., insufficient evidence-based research on toxicity data. This void in knowledge presents a promising avenue for future investigations, opening doors to expanded inquiries into the properties and potential applications of B. volubilis in the context of human diseases. Full article

The use of medicinal plants in the management of diabetes mellitus (DM) is extensively reported. However, there is still very limited information on the role of these plants as markers of oxidative stress in DM. This current review evaluated the effect of Amaranthus spinosus, Amaranthus hybridus, and Abelmoschus esculentus on markers of oxidative stress in rodent models of DM. Current findings indicate that these plants have the potential to reduce prominent markers of oxidative stress, such as serum malondialdehyde and thiobarbituric acid-reactive substances, while increasing enzymes that act as antioxidants, such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase. This may reduce reactive oxygen species and further ameliorate oxidative stress in DM. Although the potential benefits of these plants are acknowledged in rodent models, there is still a lack of evidence showing their efficacy against oxidative stress in diabetic patients. Therefore, we recommend future clinical studies in DM populations, particularly in Africa, to evaluate the potential effects of these plants. Such studies would contribute to enhancing our understanding of the significance of incorporating these plants into dietary practices for the prevention and management of DM. Full article

Mango and its by-products have traditional medicinal uses. They contain diverse bioactive compounds offering numerous health benefits, including cardioprotective and metabolic properties. This study aimed to explore the impact of mango fruit and its by-products on human health, emphasizing its metabolic syndrome components. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR were searched following PRISMA guidelines, and the COCHRANE handbook was utilized to assess bias risks. In vivo and in vitro studies have shown several benefits of mango and its by-products. For this systematic review, 13 studies met the inclusion criteria. The collective findings indicated that the utilization of mango in various forms—ranging from fresh mango slices and mango puree to mango by-products, mango leaf extract, fruit powder, and mangiferin—yielded many favorable effects. These encompassed enhancements in glycemic control and improvements in plasma lipid profiles. Additionally, mango reduces food intake, elevates mood scores, augments physical performance during exercise, improves endothelial function, and decreases the incidence of respiratory tract infections. Utilizing mango by-products supports the demand for healthier products. This approach also aids in environmental conservation. Furthermore, the development of mango-derived nanomedicines aligns with sustainable goals and offers innovative solutions for healthcare challenges whilst being environmentally conscious. Full article