Thesis (MNutr (Human Nutrition))--Stellenbosch University, 2008. / Background: Cancer patients have been documented to use complementary and alternative medicine (CAM) frequently, a subject that has been extensively researched. There is however a lack in the current literature of controlled studies that investigate the prevalence of CAM use among cancer patients compared to non-cancer controls. Aim: To assess and compare the prevalence of dietary related CAM use among adult cancer patients and non-cancer controls in the Norwich area, England. Methods: Self-administered questionnaires were used to survey cancer patients attending a comprehensive cancer centre in Norwich, and non-cancer controls attending three dental surgeries also in the Norwich area. Questions addressed patient demographics, information relating to cancer diagnosis (cancer cases only) and information on CAM use. CAM users were asked about types and duration of CAM use, reasons for use, information sources used, disclosure to health professionals, reported side effects and benefits and satisfaction with CAM therapies. Results: Questionnaires were distributed to 132 cancer cases and 126 controls, with 98 and 96 assessable replies received from the cases and controls respectively. Overall, 47% of the cancer cases used CAM, in comparison to 53% of the control group, with no significant difference (p=0.673) between the two groups. Large quantities of juice, multivitamins, fish oils and glucosamine were the most popular CAM therapies among the two groups. Usage was significantly associated with the cancer site (p=0.036) and duration of cancer diagnosis (p=0.050). Only 54% of the cancer cases and 44% of the controls informed a health professional about their CAM use. The main reasons for using CAM were to boost the immune system and to improve quality of life. Reported benefits included increased optimism and hope. Conclusions: Although CAM was commonly used by British cancer patients, there was no significant difference in comparison to the non-cancer controls. Therefore, increased awareness and knowledge of CAM use should not be limited only to those working with oncology patients, but be extended to health professionals in all patient groups.

Background: Natural products have attracted high attention due to their great contribution in drug discovery. Many natural products have shown to be effectively against different disease targets including cancer, malaria and HIV. And their structural diversity is a rich resource for the discovery of novel bioactive compounds. This thesis is to explore plant natural products for their potential in treatment of malaria and cancer diseases. Malaria is still considered as a major global health problem, affecting a large population of the world, especially in the developing countries. Effective drug discovery is still one of the main efforts to control malaria, and plant-derived compounds have played the most important role for treatment of malarial disease. In our previous work, we have evaluated more than 2,000 plant extracts against the malaria parasite Plasmodium falciparum. As a result, we discovered dozens of antiplasmodium plant leads. Bioassay guided separation of these active plant extracts led to isolation of some potent antimalarial compounds. Among them, trichothecenes, the sesquiterpenes identified from the plant Ficus fistulosa and Rhaphidophora decursiva, were found to have potent inhibitory activity against P. falciparum with IC50 values in the sub-nano molar range in our previous study (Zhang et al. 2002). However, these compounds are significant cytotoxic. In order to improve the antimalarial activity of the trichothecenes, we evaluated the antimalarial activity of dozens of trichothecenes, and based on the structure-activity relationships (SAR) analysis, we synthesized trichothecene derivatives with low cytotoxicity. On the other hand, cancer has stricken one-third of the world's population. Through our anticancer drug program to discover bioactive leads from thousands of the plant extracts, the extract of Miliusa sinensis Finet et Gagnep. (Annonaceae) was found to exhibit cytotoxic activity against a panel of cancer cell lines. Our previous bioassay-directed fractionation of the leaf, twig and flower extracts of M. sinensis has led to the discovery of a novel class of anticancer lead molecules, which we designated as miliusanes (Zhang et al, 2006). M. balansae, in the same family with M. sinensis, also contains bioactive miliusanes. We thus collected the plant materials of M. balansae to isolated additional new anticancer miliusanes. Objective: The objective of this study is to discover novel antimalarial and anticancer natural compounds from plants using different techniques in combination of extensive literature review, phytochemical separation, SAR analysis, semi-synthesis and biological activity study. Trichothecenes and miliusanes are the two major classes of the compounds, which have been extensively explored in the current thesis for their antimalarial and anticancer potential.;Methodology: There was a prior comprehensive review article entitled "Antimalarial activity of plant metabolites" by Schwikkard and Van Heerden (2002), which reported structures of those antiplasmodial active compounds and covered literatures up to the year 2000. As a continuation of their work, antimalarial compounds isolated from plants, including marine plants, which reported in the literatures from 2001 to the end of 2017 have been reviewed and organized according to their plant families. Dozens of trichothecenes have been obtained by us and explored for their SARs. Based on the SAR analysis, we designed and carried out the structure modifications of some trichothecenes. These compounds were evaluated for their antimalarial and cytotoxic activities. M. balansae, in the same genus with M. sinensis, was selected to isolate bioactive miliusanes, as well as the other active components through bioassay-guided fractionation study. Columns chromatography was used in fractionation and separation of the dichloromethane extract of M. balansae. Preparative HPLC separation and LC-MS analysis were used to speed up the isolation process. All isolates were determined for their chemical structures by spectroscopic means such as NMR and MS, and then evaluated for their anticancer potential. The isolated compounds with abundant amounts were further explored to modify their structures in order to improve their biological activities. Result: During the span of the last 17 years (2001-2017), 175 antiplasmodial compounds were discovered from plants. These active compounds were organized in our review article according to their plant families. In addition, we also included ethnobotanical information of the antimalarial plants. In order to decrease toxicity while retaining antimalarial activity of the trichothecenes, we analyzed SAR of 28 trichothecene analogues. Based on the SAR analysis, we were able to conclude that the diacetylation of C-4 and C-15, and the hydroxylation at C-3 or C-4 could significantly improve the therapeutic indices of trichothecenes. Subsequently, our synthesis of a trichothecene derivative demonstrated potent inhibitory activity against P. falciparum with an IC50 value of 10.4 nM and low toxicity against KB cells with an IC50 value of 556 nM. The separation of the dichloromethane extract of M. balansae led to the isolation of 16 new miliusanes, along with 12 known ones, and 6 flavonoids. Seven of them exhibited significant cytotoxicity against human colorectal cancer cell lines HCT116 with IC50 values in the range of 1.24 - 4.2 µM. The SAR study of the miliusanes indicated that the α,β-unsaturated ketone was the active group of but may not be the essential group responsible for the bioactivity of miliusanes. Two flavonoids that showed moderate cytotoxic activity were carried out their structure activities modification. A total of 19 derivatives have been synthesized based on the two flavonoid structures.

Leflunomide is widely prescribed for Rheumatoid Arthritis (RA) patients in China. However, a number of RA patients still demonstrated progressive bone erosion (PBE+) after receiving Leflunomide in our clinical data. Moreover, the PBE+ is predicted by high baseline serum CRP level (CRPBH). Further, the changes of serum bone resorption marker (Tartrate-resistant acid phosphatase 5b, TRAP5b) strongly correlated with those of CRP in PBE+ RA patients during Leflunomide treatment. Those were consistently observed in collagen-induced-arthritis (CIA) rats. To precisely address the issue, we screened a series of marketed drugs combined with Leflunomide to inhibit CRP production and CRP-related osteoclastic signaling pathway using bioinformatics analysis. Ligustrazine was postulated as an optimal candidate drug. In vitro studies demonstrated that the combination of Ligustrazine and Leflunomide not only suppressed hepatic CRP production, but also suppressed CRP-related osteoclastic signaling and osteoclast activities. In vivo studies showed that the combination attenuated bone erosion in CIA rats. Further, the randomized parallel controlled clinical trial in 120 CRPBH RA patients showed that the combination therapy reduced serum CRP levels and attenuated bone erosion in those patients (ChiCTR-TRC-10001014). Together, this work presents a precision combination therapy for PBE+ in CRPBH RA patients.

Diabetes mellitus is a chronic physiological carbohydrate metabolic disorder with significant impact on the economy, quality of life and life expectancy in South Africa. Herbal medicine has become the alternative therapy in the management of this disease. However, their safety and effectiveness have not been investigated. To address this, one of the plants used in Eastern Cape Province, South Africa, Bulbine abyssinica A. Rich (Asphodelaceae), was evaluated. Bulbine abyssinica is one of the species used in the management of diabetes mellitus. This plant was mentioned during an ethnobotanical survey conducted in Nkonkobe municipality of the Eastern Cape Province. Though a decoction prepared from the whole plant is used in the treatment of diabetes mellitus, the mechanism of action and its safety has not been elucidated. Thus, this research work was designed to contribute to the understanding of the possible mechanism of action of B. abyssinica as an antidiabetic medicinal plant and its toxic potentials to the users. The aqueous extract exhibited remarkable inhibitory activity onα-amylase (estimated inhibitory concentration (IC)50 value of 3.28 μg/ml), while the acetone extract exhibited weak inhibitory activity. The acetone extract exhibited notable α-glucosidase inhibitory activity (IC50 value of 4.27 μg/ml) while aqueous extract had significantly weak activity. The Lineweaver-Burk double reciprocal plots revealed that the aqueous extract exerts noncompetitive inhibition on the α-amylase activity while the acetone extract exerts a near competitive inhibitory pattern on the α-glucosidase activity. The extracts from the plant possessed high free radical scavenging activities, with acetone extract exhibiting the highest activities in all assay models used except with ferric reducing power and nitric oxide (NO) scavenging ability. The aqueous extract exhibited the highest ferric reducing power and nitric oxide radical mopping strength while the essential oil exhibited the highest scavenging activities with 1,1-diphenyl-2-picrylhydrazyl (DPPH) and relatively high ferric reducing power and nitric oxide scavenging ability. The acetone extract and the essential oil of this species exhibited higher albumin denaturation inhibition than the aqueous extract while the latter showed the greatest membrane lysis protection. The essential oil, acetone and aqueous extracts from this plant significantly inhibited the growth of Shigelle flexneri, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis. Klebsiella pneumonia, Proteus vulgaris and Streptococcus pyogens growth were inhibited by acetone and aqueous extracts. The essential oil also showed inhibitory activity against Proteus vulgaris. However, the extracts were active against the growth of only three fungi species. The essential oil showed significant inhibitory activity against Trichophyton rubrum. The aqueous extract inhibited the growth of Microsporum gypseum while the acetone extract was active against Microsporum canis, and Microsporum gypseum. The carbohydrate, crude fibre, moisture, ash, crude protein and crude fat of approximately 74.8 percent, 8.9 percent, 8.8 percent, 8 percent, 7.7 percent and 0.6 percent, respectively, were detected in this plant. The species is characterized by moderate levels of oxalates, phytic acids, Vitamin A, Vitamin C and Vitamin E. Potassium and calcium were present in highest levels, while magnesium, iron, sodium, aluminium and phosphorus were moderately present. Manganese, zinc and copper where in low amounts. These vitamins and mineral elements were within their recommended daily allowance (RDA) in humans. The investigation also revealed appreciable amounts of total phenols, flavonoids, flavanols, proanthocyanidins and alkaloids in both acetone and aqueous extracts while saponins and tannins were in trace amounts. The essential oil was characterized by large quantities of terpenes (91.9 percent) and small fraction of esters (8.01 percent).

Rheumatoid arthritis (RA), the most common autoimmune disease, affects billions of people worldwide. Conventional therapeutics do not provide satisfactory efficacy and even cause severe adverse reactions. Researchers are seeking new approaches for RA management. Toll-like receptor 4 (TLR4) signalling plays a pivotal role in the pathogenesis of RA, and has been proposed as a potential therapeutic target for RA. Chinese medicines are believed to be alternative options for conventional RA therapeutics. A herbal formula RL, consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos, has traditionally been used in treating various inflammatory disorders including RA. In this study we assessed the anti-arthritic efficacy of RL in animals, and investigated the involvement of TLR4 signalling in RL's effects in vivo and in vitro. In vivo anti-arthritic efficacy of RL was evaluated using CIA (collagen-induced arthritis) rats, a model that is well established for studying human RA. Articular disease manifestations were investigated grossly, radiographically, and histologically. Isolated splenocytes were used to determine the effects of RL on immune responses. Molecular events in the TLR4 pathways upon RL treatment were examined in sera and joint tissues of CIA rats as well as in cultured lipopolysaccharide (LPS)-stimulated murine RAW264.7 and human THP-1 cells.

中风后失语，现代医学称“急性交流障碍” ，它是急性脑血管病的常见症状之一，古代医籍中称失语为“喑痹” 、“风懿” 、“风喑” 、“风癔” 、“难言” 、“不语”等。〈素问－脉解〉云：“所谓入中为喑者’阳盛己衰，故为喑也。内夺而厥，则为喑痹。”《素问－刺禁论〉云：“……刺足少阴脉’重虚出血’为舌难以言。”《金匮要略·中风历节病脉证治〉：“邪入于腑，即不识人；邪入于脏’舌即难言’口吐涎”等。 言语障碍是脑血管疾病的常见症状，在卒中急性期，合并有失语的患者比例高达21%-38% ，据国内报道，脑血管疾病患者约25%伴有言语障碍。另外，卒中患者中除了明显失语之外，仍有60%患者在交流上存在问题。由于中风失语不仅给家庭、社会和国家带来沉重的经济负担，同时也给中风患者的身心带来了巨大伤害，故探索有效的中风失语治疗方案、提高其临床疗效、改善失语症患者的生存质量是当今亟待解决的问题。 本文对于中风后失语症的论述主要分为两大部分： 第一部分从中、西医角度认识中风后失语症。中风的病因是以正气不足、肝肾阴亏、肝阳上扰、肝风内动、血脉不通、风邪留而不去为致病之本，以风、火、痰、湿、气、血为致病之标。由此而并发的失语症主要是舌体瘫痪强直、记忆力下降健忘或认知障碍思维不清所导致，其病在心（脑），肝涉及脾、肾等脏腑。众多研究者进行了对于中风后失语症的各种治疗方法的多方面研究， 笔者收集了2010年1月至2014年12月的相失临床文献并进行了整理分析。 第二部分从针灸临床角度，对所收集到关于针灸治疗中风后失语的文献进行综合分析。运用计量学评价方法，从期刊分布、年份分布、诊断标准、随机对照、言法、脱落病例、样本量、治疗方法等多个方面， 对针灸治疗中风后失语症的研究状况做一个全面系统的分析及，并在此基础上对临床研究质量的总体水平作出评价，讨论中风后失语症的针灸临床规范研究方案，筛选有效的针灸处方，提高针灸临床科研的质量。 關键词：中风后失语症 针灸治疗

Submitted in partial compliance with the requirements of the Master’s Degree in Technology in Homoeopathy, Durban University of Technology, Durban, South Africa, 2018. / Dysmenorrhoea is the term used to describe painful menstrual cramps, and is the most commonly encountered gynaecological disorder. It affects more than 50% of women of reproductive age, of which 10% to 12% experience severe dysmenorrhoea that interferes with their daily lives by incapacitating them for 1 to 3 days each month. Dysmenorrhoea is estimated to be the single greatest cause of working hours lost by women and school absence in teenage girls (Dawood 2008; Lindeque 2015: 6-9). Primary dysmenorrhoea is defined as painful, spasmodic cramping in the lower abdomen just before and/or during menstrual bleeding, in the absence of any identifiable macroscopic pathology. It is related to increased levels of inflammatory markers such as vasopressin, prostaglandins (PGF2α) and leukotrienes from the secretory endometrium. These induce ischaemia due to excessive prolonged uterine contractions, increased the sensitivity of pain fibres, and cause vasoconstriction (Iacovides, Avidon and Baker 2015: 1-17; Stewart and Deb 2014: 296-302). This double-blinded randomised study aimed to establish the efficacy of a homoeopathic complex (consisting of Angelica sinensis 6cH, Dioscorea villosa 6cH, Matricaria chamomilla 6cH, Viburnum opulus 6cH and Zingiber officinalis 6cH) compared to a homoeopathic similimum in 30cH plussed potency in the treatment of the symptoms of primary dysmenorrhoea, in terms of the participants’ perception of the treatment. Thirty female students, who signed the inform consent forms (Appendices B and D), from the Durban University of Technology were selected based on specified inclusion and exclusion criteria after they underwent an abdominal ultrasound examination (Appendix D) by a gynaecologist. They were randomly divided by means of convenience sampling according to a randomisation sheet into two groups. There were 20 in the experimental group which received the homoeopathic complex, and 10 in the control group which received the homoeopathic similimum. The study took place at the Homoeopathic Day Clinic, located at the Durban University of Technology. It was conducted over a period of three menstrual cycles per participant. The initial consultation took place prior to a menstrual period and the subsequent three follow-ups took place once a month, a week after each menstrual period. During each consultation, a detailed homoeopathic case history was conducted and a physical examination including an abdominal examination was performed. In addition, the participants were required to complete the Moos Menstrual Distress Questionnaire (Moos 1968) (Appendix G) and the Pain Rating Scale (British Pain Society 2006) (Appendix H). SPSS version 23.0 software was used to analyse the data collected from these questionnaires. The quantitative variables across the groups were compared using the Kruskal-Wallis test since the captured data was non-parametric. The one-way analysis of variance (ANOVA) was used to compare intra-group data. Quantitative variables were expressed as a mean ± standard deviation. A p-value less than 0.05 was considered significant. The intra-group analysis using the PRS and the MDQ scales (Appendices G and H) showed statistically significant changes in the subcategories of pain in the simillimum group, while these changes were noticed in the complex group only with the PRS scale, when different follow up mean pain score was compared to that at baseline. The different comparisons and p-values can be found in the Appendix G1. The homoeopathic complex group showed more statistically significant changes in the subcategories of behaviour change, negative affect, and control (Appendix G1); while the homoeopathic similimum also revealed other statistically significant changes in the autonomic response and appetite change subgroups (Appendix G1). The inter-group analysis did not reveal any statistically significant change between the groups, although a decrease in the majority of the various mean scores was observed throughout the study. The study’s results led to the conclusion that both the homoeopathic complex and homoeopathic similimum were effective (Appendix G1) in the treatment of symptoms of primary dysmenorrhoea during various follow-ups, as well as reducing the need for allopathic pain medications in the participants during the study. However that efficacy shown by the presence of statistically significant results could not been maintained throughout the study from the baseline to the third follow-ups, this could be due to the smaller sample size of the participants, the need for a better suited similimum remedy with a higher potency for the control group; or the need for another complex remedy, It was also noted that there was no evidence that one treatment was more beneficial than the other even though a decrease in the mean scores was observed in both groups. / M

Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2017. / The continued use and popularity of plant-based traditional medicine demands scientific validation of the therapeutic potential of the medicinal plants used in disease management and treatment. These medicinal plants are to be evaluated for phytochemical constituents and pharmacologically screened for their bioactivity and include the isolation and identification of their bioactive compounds. The diabetes tea and its eight individual plants constituents were collected from Sing Fefur Herbs in McGregor, Western Cape. The plant material was ground to a fine powder form using a milling machine. The powdered plant material was sequentially extracted with hexane, 1:1 DCM, DCM:MeOH, MeOH and water. The antioxidant activity of the tea and its plants was evaluated with comparison to the antioxidant activity of brewed rooibos tea in literature. The concentration of antioxidants in the plants and the tea were found to be significantly high. The ORAC assay results of the water extracts were significantly higher than that of rooibos tea in all plants. Salvia africana-caerulea water extract ORAC results were 14147.10±1.02 μmol TE/g and this is 10 times better than the brewed rooibos tea results of 1402±44.1 μmol TE/g. The alpha-amylase enzyme inhibition assay showed no significant results while the alpha-glucosidase enzyme inhibition assays showed significant results in some of the extracts. The highest inhibitory activity towards alpha-glucosidase was found in the Urtica urens hexane extract and the Thymus vulgaris hexane extract (69.66% and 68.43%, respectively). This observation suggests that alpha-glucosidase enzyme is inhibited mostly by the less polar or medium polarity chemical components of the plant extracts. The crude plant extracts that showed significant activity in the antidiabetic bioassays were further subjected to cytotoxicity assay to ascertain the safety of extracts. The T. vulgaris DCM extract, Salvia officinalis DCM extract and Salvia officinalis hexane extract showed a cell growth inhibition of 54.91%, 62.14% and 63.87% at 100 μg/ml, respectively. The Salvia africana-caerulea DCM extract showed a cell growth inhibition of 59.10% at 50 μg/ml and 62.14% at 100 μg/ml. In the cytotoxicity analysis Salvia africana-caerulea DCM extract is the only extract that showed cell viability below 50% for both concentrations. Phytochemical screening of selected methanolic and aqueous extracts of the diabetes tea and the Salvia africana-caerulea showed the presence of alkaloids, sugars, flavonoids, glycosides, proteins & amino acids, phenolics & tannins and saponins. Furthermore isolation, purification and analysis of two Salvia africana-caerulea crude extracts (DCM and DCM:MeOH) were done in order to try and obtain pure compounds. The compound characterization was done through the use of chromatographic techniques. Thin layer chromatography (TLC), flash chromatography and column chromatography resulted in the generation of 29 fractions. Spectroscopic techniques utilized for chemical structural elucidation for compounds of interest included Liquid chromatography mass spectrometry and Nuclear Magnetic Resonance Spectroscopy. Of all the fractions generated, DM 23 was the purest and its structural elucidation was attempted.

Currently, the approved anti-HIV drugs on the market only target the three HIV enzymes: reverse transcriptase, protease and more recently, integrase. Due to the limited nature of the current therapy, it is possible that a multi-drug resistant virus can emerge. The main concerns in developing countries however, are the expense and availability of the drugs and because of this, it is essential to investigate all alternatives. Traditional medicine offers many advantages as compared to allopathic treatment in so far as being relatively cheaper, accessible and it is broadly accepted in the population groups of the developing countries. Little is known though, of the exact efficacy and toxicity of these remedies so it is vital that these possible leads be investigated thoroughly. For the purpose of this study, two plants, Sutherlandia frutescens and Lobostemon trigonum were studied to ascertain their potential anti-HIV activity. Sutherlandia has received international attention as a possible cheap herbal remedy to improve the health of AIDS sufferers. Anecdotal evidence from health workers claim that HIV- infected patients on Sutherlandia treatment have shown improved CD4 counts, decreased viral loads and a general improvement in well-being. Extracts were prepared from dried leaves and flowers in methanol, ethanol, acetone, methylene dichloride or distilled water. Sulphated polysaccharides have been described extensively in literature with regards to their anti-HIV activity, so as a form of dereplication; an ethanol precipitation was performed on the aqueous extracts to remove sulphated polysaccharides. A toxicity study was performed on all crude extracts using uninfected peripheral mononuclear blood cells (PBMCs) isolated from whole blood. To measure anti-HIV activity, HIV-infected PBMCs were cultured with each of the crude extracts and cell viability measured using the tetrazolium salt, XTT. HIV-infected CEM-NKR-CCR5 cells were also used and supernatant from the viral studies was tested for the HIV antigen p24. xii Results varied greatly between assays but with the inclusion of a point-scale system to evaluate the extracts it was clear that overall the organic extracts of the Sutherlandia flowers, especially the acetone extract (SFA), showed great anti-HIV potential. SFA in every case decreased p24 levels and in the toxicity study did not decrease cell proliferation. With the HIV-infected PBMCs SFA actually helped improve cell proliferation despite the infection. To determine the specific anti- HIV activity, all crude extracts were tested for inhibition of HIV-I reverse transcriptase, the glycohydrolase enzymes: a-glucosidase, ß-glucosidase, ßglucuronidase, HIV-I integrase and HIV-II protease. No significant inhibition was seen with these experiments except for the HIV-I RT assay. The aqueous extract of the Lobostemon leaves produced an inhibitor of HIV-RT with a very low IC50 value of 0.049mg/ml. Some inhibitory effect was lost with the removal of the sulphated polysaccharides and the addition of BSA to the assay, but still 64% inhibition of the HIVRT remained, which confirmed that the inhibitor could be something novel, and not of the polysaccharide or tannin compounds.

A herbal formula (SL) comprising edible Sophorae Flos and Lonicerae Japonicae Flos was used to treat melanoma in ancient China. In current Chinese medicine practice, the two ingredient herbs of SL are commonly prescribed by Traditional Chinese medicine (TCM) doctors for treating melanoma. However, there is no modern clinical or experimental evidence about the anti-melanoma actions of this formula. Signal transducer and activator of the transcription (STAT3), which is constitutively activated in melanoma, has been proposed as one of the anti-melanoma targets. Some natural compounds in SL have been shown to assault cancers including melanoma via inhibiting STAT3 signaling. In this study, we investigated the anti-melanoma effects and explored STAT3 signaling-related mechanism of action of SL. We also identified bioactive components responsible for SL's anti-melanoma effects. Our in vitro and in vivo studies showed that SLE, an ethanolic extract of SL, induced apoptosis, inhibited proliferation, migration and invasion in melanoma cells, inhibited melanoma growth, angiogenesis and prolonged host survival in melanoma-bearing mice. SLE significantly suppressed the activation of STAT3 and its upstream kinase Src in both mouse melanoma tissues and cultured melanoma cells. In melanoma cells, we also found that SLE restrained STAT3 nuclear localization and inhibited the expression of STAT3-regulated genes related to melanoma growth, metastasis and angiogenesis. Overactivation of STAT3 in A375 human melanoma cells diminished the anti-proliferative, pro-apoptotic and anti-invasive effects of SLE. RNA-seq and small RNA sequencing analyses showed that SLE altered both the gene expression profile and miRNA signature in B16F10 melanoma tissues. Based on the RNA-seq data, we further validated that SLE inhibited the IL-17-IL-6-STAT3 axis in melanoma. Verification assays for the candidate miRNAs suggested that the significantly upregulated miR-205-5p is a possible target of SLE. Enforced miR-205 expression has been shown to suppress EMT in melanoma cells. In this study, we demonstrated that SLE inhibited melanoma cell EMT, and miR-205-5p knockdown diminished this effect of SLE. In addition, we computationally demonstrated that luteolin, a naturally occurring edible flavone abundant in Lonicerae Japonicae Flos, could directly bind to Src kinase domain. Experimentally, we verified that luteolin inhibited the Src/STAT3 signaling in both melanoma cells and tissues. In addition to inhibit STAT3 activation, luteolin promoted ubiquitin-proteasome pathway-mediated degradation of STAT3. Luteolin also exerted evident in vitro and in vivo anti-melanoma effects, and overactivation of STAT3 diminished its anti-melanoma effects. In conclusion, we demonstrated that SLE exerted in vivo and in vitro anti-melanoma effects, and inhibition of Src/STAT3 signaling and elevation of miR-205-5p expression contributed to these effects. Luteolin was identified to be one of the active components responsible for the inhibitory effects of SLE on STAT3 signaling and the anti-melanoma effects of SLE. This study provides a pharmacological and chemical basis for the traditional use of the formula SL in treating melanoma, and suggests that SLE and SLE-derived compounds have the potential to be developed as modern alternative and/or complimentary agents for melanoma management.