Botanical Formula Research Articles

Prevention of Bladder Cancer Recurrence With the Botanical Formula LCS103: A Case Series Study.

Despite effective chemotherapy and other available oncology treatments, recurrence rates for non-muscle invasive bladder cancer (NMIBC) remain high, with as many as 60% of patients requiring repeat intravesical treatments with BCG or other agents within a 24-month period. The botanical formula LCS103 has displayed anti-cancer activity on bladder cancer cells, though its clinical efficacy remains to be proven. A consecutive series of 30 patients with bladder cancer was examined retrospectively, of which a cohort of 20 patients (18 with NMIBC, 2 with metastatic disease) was treated with LCS103 for between 14 months and 16 years, in addition to their conventional oncology care. Only 3 patients (15%) had a single tumor recurrence after initiation of the botanical treatment, as opposed to pre-treatment recurrence reported among 11 patients (55%; range, 1-5). The majority of LCS103-treated patients reported reduced severity for urological symptoms (pain, frequency, and urgency on urination; and nocturia), as well as for weakness and fatigue, and for general wellbeing. No adverse events were associated with use of the botanical formula. Further prospective randomized trials are needed to confirm and better understand these initial findings.

Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota.

Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are urgently needed. We studied the botanical formula "Li-Hong Tang (LHT)", which contains two main ingredients, Salvia plebeia R. Br and Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba. In this study, we aimed to identify the effects of LHT on UC and explore its potential mechanism. LHT was analyzed using a mass spectrometer (MS). DSS at a dose of 2.5% was utilized to develop UC in mice. The administered groups received low, medium, and high dosages (0.32g/kg, 0.64g/kg, and 1.28g/kg) of LHT and the positive medication, sulfasalazine (0.2g/kg), respectively. Body weight, disease activity index (DAI) score, colon length, spleen index, serum myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD) and inflammatory factor concentrations were monitored. The expression of NRF2 and HO-1 in colonic tissues was evaluated by immunohistochemistry. 16S rDNA sequencing was employed to investigate alterations in the gut microbiota of the mice, aiming to elucidate the extent of LHT's impact. LHT may ameliorate DSS-induced colitis in mice by lowering inflammation, reducing oxidative stress, restoring the intestinal barrier, and influencing the NRF2/HO-1 pathway. Moreover, LHT treatment exhibited a regulatory effect on the gut microbiota, characterized by elevated levels of Patescibacteria, Verrucomicrobiota, Candidatus_Saccharimonas, Lactobacillus, and Ligilactobacillus levels while decreasing Oscillibacter and Colidextribacter levels. Further study indicated that MPO, NO, and inflammatory factors were positively correlated with Oscillibacter, Colidextribacter, Escherichia-Shigella, Anaerostines, and negatively with Lactobacillus, Clostridiales_unclassified, Candidatus_Saccharimonas, and Patescibacteria. Furthermore, colony network analysis revealed that Lactobacillus was negatively associated with Oscillibacter and Colidextribacter, whereas Oscillibacter was positively related to Colidextribacter. LHT protects against DSS-induced mice by inhibiting the inflammatory response, oxidative stress, and mucosal injury. The protective role may involve regulating the NRF2/HO-1 signaling pathway and gut microbiota.

Efficacy of a commercial mixed botanical formula in treatment and control of coccidiosis in poultry

Coccidiosis, a protozoal disease caused by a species of the Eimeria genus, causes tremendous economic damage to the poultry industry. Numerous natural remedies have been developed to combat emerging drug-resistant Eimeria species and mitigate public concerns about anticoccidial drug residues in poultry products. In the current study, the anticoccidial efficacy was evaluated of a commercial mixed botanical product, administered in two concentrations, in the treatment and control of a mixed coccidian infection. In this respect, 120 newly hatched broiler chickens were randomly allocated into five equal groups: Cox500, Cox1000, Positive control (PC), Negative control (NC), and Control (C). The first three groups were exposed to oocysts of several Eimeria species, Cox500 and Cox1000, and then received the two concentrations of a botanical blend (500 and 1,000 ml of formula per 1,000 L of drinking water, respectively) for five consecutive days. The positive control also received toltrazuril (7 mg/kg of live weight) through drinking water for two consecutive days. The negative control and control were the challenged-unmedicated and unchallenged-unmedicated groups, respectively. The chicks were monitored for clinical signs, intestinal lesions, performance indices, and oocyst shedding. The results indicated that the tested botanical formula in both concentrations improved the growth performance of the birds. However, the higher concentration prompted lower oocyst shedding and, likewise, toltrazuril in the positive control, healed cecal lesions more rapidly. In summary, the blended botanical formula, particularly in the higher concentration (1,000 ml per 1,000 L of drinking water), could successfully be incorporated into therapeutic strategies against coccidiosis in broiler flocks.

Beyond the Hot Comb: Updates in Epidemiology, Pathogenesis, and Treatment of Central Centrifugal Cicatricial Alopecia from 2011 to 2021.

Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia that predominantly affects middle-aged women of African descent. Recent data suggest a multifactorial etiology of CCCA that is influenced by environmental and genetic factors. Emerging evidence regarding the genetic basis of the condition may elucidate new therapies. While topical and intralesional steroids and tetracycline antibiotics are the mainstay of treatment, refractory cases may be considered for hair transplantation. Emerging therapies using platelet-rich plasma, botanical formulas, and cosmetic procedures have shown promising results for the future management of CCA. As recent notable advances in CCCA have been achieved, this review provides an update on the epidemiology, pathophysiology, and management of CCCA.

Efficacy and Safety of a Botanical Formula Fuzheng Huayu for Hepatic Fibrosis in Patients with CHC: Results of a Phase 2 Clinical Trial.

Background Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia. Method We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n = 59) or placebo (n = 59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules. Results FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0–F2 (p=0.03). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage. Conclusions FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.

In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology approach and molecular docking in silico were applied to uncover the potential multicomponent synergetic effect and molecular mechanisms. The targets of ingredients in GQD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM) database, while the UC targets were retrieved from Genecards, therapeutic target database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The topological parameters of Protein-Protein Interaction (PPI) data were used to screen the hub targets in the network. The possible mechanisms were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the active compounds and hub targets. Network pharmacology analysis successfully identified 77 candidate compounds and 56 potential targets. The targets were further mapped to 20 related pathways to construct a compound-target-pathway network and an integrated network of GQD treating UC. Among these pathways, PI3K-AKT, HIF-1, VEGF, Ras, and TNF signaling pathways may exert important effects in the treatment of UC via inflammation suppression and anti-carcinogenesis. In the animal experiment, treatment with GQD and sulfasalazine (SASP) both ameliorated inflammation in UC. The proinflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by UC were significantly decreased by GQD and SASP. Moreover, the protein expression of EGFR, PI3K, and phosphorylation of AKT were reduced after GQD and SASP treatment, and there was no significance between the GQD group and SASP group. Our study systematically dissected the molecular mechanisms of GQD on the treatment of UC using network pharmacology, as well as uncovered the therapeutic effects of GQD against UC through ameliorating inflammation via downregulating EGFR/PI3K/AKT signaling pathway and the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6.

A novel botanical formula improves eye fatigue and dry eye: a randomized, double-blind, placebo-controlled study

With the frequent use of video display units, eye fatigue is becoming more common globally. An alternative nutritional strategy is needed to prevent the aggravation of eye fatigue symptoms. The objective was to evaluate the protective effect of a novel botanical combination of lutein ester, zeaxanthin, and extracts of blackcurrant, chrysanthemum, and goji berry on adults with eye fatigue in a randomized, double-blind, placebo-controlled clinical trial. We randomly allocated 360 participants into 4 groups to receive placebo and 3 doses of our formula (chewable tablets, containing 6 mg, 10 mg, or 14 mg of lutein) once daily for 90 d. Each participant had 3 visits at baseline (V1), 45 d (V2), and 90 d (V3) during the study. Intervention with the formula improved individual scores of eye fatigue symptoms, including eye soreness, blurred vision, dry eye, foreign body sensation, and tearing. Compared with placebo, the formula at all 3 doses significantly decreased the total score of eye fatigue symptoms and increased the visuognosis persistence time at both V2 and V3. According to the Schirmer test, both 10-mg and 14-mg lutein formula groups had improved tear secretion at V3 compared with the placebo. The keratography results indicated that the first tear break-up time, average tear break-up time, and tear meniscus height were significantly increased after formula intervention. The formula at all 3 doses significantly increased the macular pigment optical density at V2 and V3 compared with the placebo, whereas optical coherence tomography showed no significant difference in retinal thickness and retinal volume across all groups at both visits. Our botanical formula improves eye fatigue, dry eye, and macular function without changing the retinal structure, and thus it could serve as an effective nutritional strategy in improving eye fatigue without causing serious side effects.Clinical Trial Registry: chictr.org.cn (ChiCTR1800018987).

Effect of the botanical compound LCS102 on innate immunity.

Innate immunity serves an important role in the healthy population, providing surveillance and protection against infections. Chemotherapy suppresses the body's immune system, including neutrophil and natural killer (NK) cell numbers and activity. This leads to an increased risk of infection which often requires the reduction or even discontinuation of the chemotherapeutic regimens. The botanical formula LCS102 was designed to stimulate the body's immune system. The effect of the formula on innate immunity was examined in human blood samples, as were its effect on the anti-cancer activity of chemotherapeutic agents on human cancer cells. Blood samples drawn from 20 volunteers (19 healthy subjects; 1 patient with breast cancer undergoing chemotherapy) and were exposed to LCS102. The effects on neutrophil and NK cell activity were tested using FACS. The anti-cancer effects of LCS102 were tested on T24, A549, MCF7, PANC-1 and U2OS human cancer cell lines, as were the effects of the formula on doxorubicin, Taxol, etoposide and cisplatin-treated cells using a sulforodamine B viability assay. LCS102 was shown to significantly increase the percentage of activated neutrophils and NK cells in the blood samples tested. The formula did not inhibit the cytotoxic effects of the chemotherapeutic agents, and in certain cases increased their anti-cancer activity. Further research is required to improve our understanding of the clinical value of LCS102; however, it may serve as an adjuvant during chemotherapy, to reduce the effects of chemotherapy on innate immunity.

Efficacy Evaluation and Dose Prediction of a Novel Botanical Formula on Eye Fatigue and Dry Eye to Provide a Personalized Nutrition Solution

Abstract Objectives With the frequent use of video display units, eye fatigue is more and more common globally. We aimed to evaluate the protective effect of a novel botanical combination of lutein ester, zeaxanthin, extracts of black currant, chrysanthemum and goji berry on adults with eye fatigue in a randomized controlled trial, and predict personalized dose for each individual in real-life consumption. Methods 360 participants were randomized to receive our formula with 3 different doses (containing 6 mg, 10 mg, and 14 mg of lutein, respectively) or placebo once daily for 90 days. Each participant had a total of 3 visits at baseline (V1), 45 days (V2) and 90 days (V3) throughout the study. Results The formula intervention improved individual score of eye fatigue symptoms, including eye soreness, photophobia, blurred vision, dry eye, foreign body sensation and tearing. Compared with placebo, the formula with all 3 doses significantly decreased the total score of eye fatigue symptoms and increased the visuognosis persistence time at both V2 and V3. For Schirmer test, the formula with 10 mg and 14 mg of lutein improved the tear secretion at V3. For Keratography, first tear break time, average tear break time and tear meniscus height were significantly increased after formula intervention. The intervention of formula with all 3 doses significantly increased macular pigment optical density at V2 and V3, while optical coherence tomography showed that there was no significant difference in retinal thickness and retinal volume among all groups at both visits. Different machine-learning algorithms were used to predict personalized dose based on the eye-related indexes and other features, such as anthropometrics, physical activity, dietary habit, and blood biomarkers under 3 different dosages. Among them, XGBoost performed best with R = 0.649 for training set, R = 0.638 for test set, and R = 0.685 for external validation set. Conclusions The formula improves eye fatigue, dry eye, and macular function without changing the structure, providing a nutritional alternative strategy. XGBoost could successfully predict dose to provide a personalized nutrition solution. Funding Sources This study was supported by National Key R&D Program of China and Nutrition Research Foundation of Chinese Nutrition Society.

Effect of the botanical formula LCS101 on the anti-cancer effects of radiation therapy.

The botanical formula LCS101 has been shown in clinical research to reduce chemotherapy-induced toxicities. In pre-clinical research, the formula demonstrated selective anti-cancer effects, in part as a result of radical oxygen species (ROS) activity of the botanical components. The present study examined the interaction between LCS101 and radiation therapy on cancer cell lines. Incremental doses of LCS101 were added to breast adenocarcinoma (MCF7), prostate (DU145), transitional cell bladder carcinoma (T24), pancreatic epithelioid carcinoma (PANC-1), and osteosarcoma (U20S) cell lines 4h after single-dose irradiation (range 0.5-4Gy). Cell viability was tested using sulforhodamine B (SRB) assay after 1week, with ROS activity examined using 1mM of the ROS scavenger sodium pyruvate (ROS scavenger), testing cell viability with an SRB assay. The addition of LCS101 to MCF7 (breast) and DU-145 (prostate) cancer cell lines resulted in a dose-dependent increase in the antiproliferative effects of radiation treatment. The addition of pyruvate inhibited radiation-induced cell death in all of the cell lines treated with LCS101. The addition of the botanical formula LCS101 to irradiated cancer cells results in an apparent additive effect, most likely through a ROS-mediated mechanism. These findings support the use of LCS101 by patients undergoing radiation therapy, for both its clinical as well as anti-cancer effects.

Inhibition of Osteoarthritis-Related Molecules by Isomucronulatol 7-O-β-d-glucoside and Ecliptasaponin A in IL-1β-Stimulated Chondrosarcoma Cell Model.

Osteoarthritis (OA) is the common form of arthritis and is characterized by disability and cartilage degradation. Although natural product extracts have been reported to have anti-osteoarthritic effects, the potential bioactivity of Ryupunghwan (RPH), a traditional Korean medicinal botanical formula that contains Astragalus membranaceus, Turnera diffusa, Achyranthes bidentata, Angelica gigas, Eclipta prostrata, Eucommia ulmoides, and Ilex paraguariensis, is not known well. Therefore, the inhibitory effects of single compounds isolated from RPH on the OA-related molecules were investigated using IL-1β-stimulated chondrosarcoma SW1353 (SW1353) cell model. Two bioactive compounds, isomucronulatol 7-O-β-d-glucoside (IMG) and ecliptasaponin A (ES) were isolated and purified from RPH using column chromatography, and then the structures were analyzed using ESI-MS, 1H-NMR, and 13C-NMR spectrum. The expression or amount of matrix metalloproteinase 13 (MMP13), COX1/2, TNF-α, IL-1β or p65 was determined by RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA). RPH pretreatment reduced the expression and amounts of MMP13, and the expression of collagen II, COX1/2, TNF-α, IL-1β or p65, which were increased in IL-1β-stimulated SW1353 cells. IMG reduced the expression of all OA-related molecules, but the observed inhibitory effect was less than that of RPH extract. The other single compound ES showed the reduced expression of all OA-related molecules, and the effect was stronger than that in IMG (approximately 100 fold). Combination pretreatment of both single components remarkably reduced the expression of MMP13, compared to each single component. These synergic effects may provide potential molecular modes of action for the anti-osteoarthritic effects of RPH observed in clinical and animal studies.

Botanical Formula LCS101: A Multi-Targeted Approach to Cancer Care.

Background and Purpose: LCS101 is a botanical formula extracted from 14 botanical components. While conventional oncology focuses on targeted medicine, research on LCS101 adopts a multi-targeted approach, examining its preclinical (in vitro, in vivo, and ex vivo) and clinical (randomized controlled trial, pragmatic) effects. This includes examining the formula’s impact on the immune system, selective anticancer effects, and improved chemotherapy-related symptoms and quality of life. Effects on the Immune System: In murine splenic cell cultures, LCS101 significantly increased T-cell proliferation and macrophage tumor necrosis factor-α production. Blood samples from healthy volunteers exposed to LCS101 showed a dose-dependent increase in natural killer cell activity; and a randomized controlled trial showed significantly lower rates of leucopenia/neutropenia and anemia in patients with breast cancer undergoing chemotherapy. Selective Anticancer Effects: In vitro LCS101 demonstrated selective growth inhibition (on XTT viability assay) in human breast and prostate cancer cell lines, without any harmful effects on normal human epithelial cells. The anticancer effects were attributed to reactive oxygen species activity. Cytotoxic effects of doxorubicin and 5-fluorouracil on breast cancer cell lines were significantly increased following exposure to LCS101, with a protective effect in normal cells. Symptom Relief and Quality of Life: Clinical research shows that patients taking LCS101 during chemotherapy are less likely to report symptoms such as fatigue, pain, nausea and vomiting. Conclusion: LCS101 exhibits multi-targeted effects, with significant implications for cancer care. Further research is needed to better understand the impact of these findings.

A novel botanical formula prevents diabetes by improving insulin resistance

BackgroundType 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China. Individually, fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root can improve glycemia in various animal models and humans with impaired glucose metabolism and T2DM. The aim of this study was to design an optimized botanical formula containing these herbal extracts as a nutritional strategy for the prevention of insulin resistance and T2DM.MethodsCell-free α-amylase and α-glucosidase enzyme assays were used to determine inhibitory potential of extracts. Glucose uptake was examined in differentiated human adipocytes using radiolabeled 2-deoxyglucose. Male Sprague Dawley rats were divided and glycemia balanced into 5 groups: two controls (naïve and model) and three doses of the botanical test formula containing standardized fenugreek seed, mulberry leaf and American ginseng extracts (42.33, 84.66 and 169.33 mg/kg BW). Insulin resistance and T2DM was induced by feeding animals a high fat diet and with an alloxan injection. Glucose tolerance was examined by measuring serum glucose levels following an oral glucose load.ResultsFenugreek seed and mulberry leaf dose dependently inhibited α-amylase (IC50 = 73.2 μg/mL) and α-glucosidase (IC50 = 111.8 ng/mL), respectively. All three botanical extracts improved insulin sensitivity and glucose uptake in human adipocytes, which lead to the design of an optimized botanical test formula. In a rat model of insulin resistance and T2DM, the optimized botanical test formula improved fasting serum glucose levels, fasting insulin resistance and the development of impaired glucose tolerance. The reduction in epididymal adipose tissue GLUT4 and PDK1 expression induced by high fat diet and alloxan was blunted by the botanical test formula.ConclusionsA novel botanical formula containing standardized extracts of mulberry leaf, fenugreek seed and American ginseng at a ratio of 1:1.3:3.4 prevented the development of insulin resistance, impaired glucose tolerance and T2DM. Given the rising need for effective non-drug targeting of insulin resistance and progression to T2DM, complementary and alternative nutritional strategies without intolerable side effects could have meaningful impact on metabolic health and diabetes risks.

First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer

Preclinical studies showed a Chinese botanical formula, PHY906, has synergistic anti-tumor activity with capecitabine. Our phase I study determined maximal tolerated dose of capecitabine 1,500mg/m(2) BID day 1-7 and PHY906 800mg BID day 1-4 every 2weeks. We conducted this phase II study to explore the efficacy of capecitabine and PHY906 in patients with advanced pancreatic cancer who were previously treated with gemcitabine-based regimens. Patients with pancreatic cancer and an Eastern Cooperative Oncology Group performance status of 0-2 received PHY906 and capecitabine. Toxicity was assessed per NCI-CTCAE v3.0 and response per response evaluation criteria in solid tumors q 6weeks. Correlative studies of cytokines, chemokines and growth factors were tested using a cytometric bead array. Quality of life was assessed by utilizing Edmonton symptom assessment system. The primary objective was overall survival. The study enrolled 25 patients. Median progression-free survival (mPFS) was 10.1weeks (range 0.4-54.1) and median overall survival (mOS) was 21.6weeks (range 0.4-84.1). Eighteen patients received at least 2 cycles, and achieved mPFS of 12.3weeks and mOS of 28weeks. Six-month survival rate was 44% (11/25). Unsupervised clustering of patients grouped those with shortened survival together by their cytokine profile showed that only IL-6 had a significant difference (p<.001) between short- and long-term survivors. Capecitabine plus PHY906 provides a safe and feasible salvage therapy after gemcitabine failure for APC. Role of IL-6 in tumor progression and tumor cachexia needs to be investigated with respect to its relation to pathophysiology of pancreatic cancer and development of anti-IL-6 therapeutics.

Tibetan Medicine: An Effective Botanical Supplement for Peripheral Vascular Circulation

This review provides an instructive example of how a botanical and mineral formula known in the tradition of Tibetan medicine as Gabyr-Nirynga (camphor combination), denoted as formula No. 28, has evolved into a contemporary application through scientific research. This developmental pathway has led to a standardized nutraceutical with clinically proven efficacy in alleviation of a form of atherosclerosis-peripheral arterial disease (PAD). The systematic scientific research began in Switzerland in 1970s and resulted in five, double-blind clinical studies conducted in various European countries on cardiovascular use of the formula. The formula’s mechanism of action has been described in Tibetan tradition based on its three groups of botanical and mineral ingredients: (1) main active ingredients, (2) auxiliary ingredients, and (3) components that offset the action of the first two groups and facilitate gastrointestinal absorption of the formula. Based on preclinical and clinical studies, several mechanisms of action relevant to alleviation of the PAD have been discussed, such as an increase in the threshold for platelet aggregation, lower total blood cholesterol and low-density lipoproteins (LDL), and prevention of blood lipid peroxidation. A study in an animal model of CNS inflammation, i.e. Experimental Allergic Encephalomyelitis (EAE), has shown that No. 28 can exert action as a biological response modifier improving response of the organism to chronic inflammation. This latter mechanism may be particularly relevant to the clinical benefits with No. 28 in patients with PAD, in view of cardiovascular disease increasingly considered as an outcome of a chronic inflammatory process. The integration of traditional knowledge of a botanical formula with science-derived pharmacology is referred in this paper as the Interactive Nutrients process.

Phase II study of PHY906 plus capecitabine (CAP) in pts with gemcitabine-refractory pancreatic cancer (PC) and measurement of cytokines.

e14540 Background: Oral CAP offers convenience as a palliative chemotherapeutic option, however, diarrhea and HFS may compromise its efficacy. Pts in USA cannot tolerate CAP 1,250 mg/m2 BID D1-14 without experiencing toxicities. PHY906, a traditional Chinese botanical formula has shown synergistic anti-tumor activity with CAP as well as cytoprotective anti-diarrheal effect in preclinical and phase I studies (ASCO 2007, 2008). These data provide a strong rationale for extending this combination into PC. Methods: PC pts with prior gemcitabine received CAP 1,500 mg/m2 BID D1-7 and PHY906 800 mg/m2 BID D1-4 q 2 wks. AEs were assessed per NCI CTCAE v3.0 and response per RECIST q 6 wks. Primary objective was OS and secondary aim to determine effect of PHY906 on cytokines and chemokines including IL-2, IL-4, IL-5, IL-6, IL-10, MCP-1, TNF-a, IFN-g, VEGF, FGF-B, GM-CSF, G-CSF using a cytometric bead array assay. Results: Twenty-five pts were enrolled: 25 received study drug (evaluable for safety); 23 received at least 1 cycle (evaluable for efficacy). Median age was 60yr (range 45-84), 10 F and 15 M, with a median ECOG PS of 1 (range 0-2). Predominant AEs included grade 3 diarrhea (n = 3), grade 3 fatigue (n = 3) and grade 3 HFS (n = 1). Among 23 pts, 2 achieved PR (9%), 10 had stable disease (43%) resulting in disease control rate of 52%. All intent-to-treat pts reached mPFS of 10 wks (r: 0.4-51) and mOS of 12 wks (r: 0.4-63). For 18 pts who received > = 2 cycles, mPFS was 13 wks and mOS 31 wks. 9-mth survival rate was 22%. Preliminary correlative studies showed that none of the cytokines except serum IL-6 was reversely correlated with survival. QOL data is currently under evaluation. Conclusions: This is the first clinical study to evaluate a botanical drug PHY906 plus CAP in PC. Our results suggest that PHY906 can increase therapeutic index of CAP by reducing diarrhea and HFS. This combination appears a safe and feasible salvage therapy after gemcitabine failure and warrants further investigation in a randomized study against CAP. Recent studies have indicated role of IL-6 in tumor progression and tumor cachexia, suggesting a need to investigate its relation to pathophysiology of PC and development of anti-IL-6 therapeutics. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PhytoCeutica PhytoCeutica Bayer, Bristol-Myers Squibb, Genentech, Novartis, Roche, sanofi-aventis Enzon, Merck, PhytoCeutica, Roche, Taiho Pharmaceutical

The influence of traditional herbal formulas on cytokine activity

Many of the botanical “immunomodulators”, a class of herbal medicines widely recognized in traditional medical systems such as Chinese Medicine (TCM) and Ayurvedic Medicine, alter immune function and may offer clinically relevant therapeutics or leads to therapeutics. Many of these traditional remedies are prepared from combinations of medicinal plants which may influence numerous molecular pathways. These effects may differ from the sum of effects from the individual plants and therefore, research demonstrating the effects of the formula is crucial for insights into the effects of traditional remedies. In this review we surveyed the primary literature for research that focused on combinations of medicinal plants and effects on cytokine activity. The results demonstrate that many extracts of herb mixtures have effects on at least one cytokine. The most commonly studies cytokines were IL-4, IL-6, IL-10, TNF and IFN-γ. The majority of the formulas researched derived from TCM. The following formulas had activity on at least three cytokines; Chizukit N, CKBM, Daeganghwal-tang, Food Allergy Formula, Gamcho-Sasim-Tang, Hachimi-jio-gan, Herbkines, Hochuekki, Immune System Formula, Jeo-Dang-Tang, Juzen-taiho-to, Kakkon-to, Kan jang, Mao-Bushi-Saishin-to, MSSM-002, Ninjin-youei-to, PG201, Protec, Qing-huo-bai-du-yin, Qingfu Guanjieshu, Sambucol Active Defense, Seng-fu-tang, Shin-Xiao-Xiang, Tien Hsien, Thuja formula, Unkei-to, Vigconic, Wheeze-relief-formula, Xia-Bai-San, Yangyuk-Sanhwa-Tang, Yi-fey Ruenn-hou, and Yuldahansotang. Of the western based combinations, formulas with Echinacea spp. were common and showed multiple activities. Numerous formulas demonstrated activity on both gene and protein expression. The research demonstrates that the reviewed botanical formulas modulate cytokine activity, although the bulk of the research is in vitro. Therapeutic success using these formulas may be partially due to their effects on cytokines. Further study of phytotherapy on cytokine related diseases/syndromes is necessary.

Screening the Efficacy of an Ayurvedic Botanical Formula: “Shothahara Compound” through Scientific and Philosophical Approaches

Screening the Efficacy of an Ayurvedic Botanical Formula: “Shothahara Compound” through Scientific and Philosophical Approaches

Review of a Treatment for Psoriasis Using Herose, a Botanical Formula

This study was undertaken to assess the efficacy of the herose formula as a treatment for psoriasis patients who have been previously treated with immunosuppressants. The study was an open one conducted in one center. Fifteen patients were instructed to take four herose capsules (450 mg per capsule) three times a day for 10 months. At each visit the investigator assessed each patient's PASI and therapeutic response to the treatment. The patients were treated and observed from February of 2004 to November of 2004. The results showed that the herose capsule may be an effective and safe treatment for moderate to severe plaque psoriasis.

Safety of a Novel Botanical Extract Formula for Ameliorating Allergic rhinitis. Part II

Each year more than 50 million Americans suffer from allergic rhinitis, which is a state of hypersensitivity or hyperimmunity. Basically, allergic rhinitis is symptomatically recognized as the inflammation and irritation of the nasal mucosal membranes; sneezing; stuffy/runny nose; nasal congestion; and itchy; watery, and swollen eyes; and defined as a state of hypersensitivity/ hyperimmunity caused by exposure to a particular allergen (antigen) that results in increased reactivity upon subsequent exposure. A novel polyherbal formulation (Aller-7/NR-A2) was developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants, including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum. Earlier studies in our laboratories have demonstrated potent antihistaminic, anti-inflammatory, antispasmodic, antioxidant, and mast-cell stabilization activities of Aller-7 in addition to its efficacy in a clinical setting. A series of preliminary toxicological evaluations were also conducted in the past, which demonstrated its safety. In this study, we have conducted further safety studies on Aller-7, including acute oral, acute dermal, acute dermal irritation, eye irritation, and 90-day repeated dose toxicity studies. Acute oral toxicity of Aller-7 was found to be greater than 5,000 mg/kg body weight in both male and female rats and no mortality or toxicity was observed at this dose, while the acute dermal toxicity was found to be greater than 2,000 mg/kg body weight. In the acute dermal irritation study, the skin irritancy index was found to be 0.0, which classifies Aller-7 as a nonirritant to rabbit skin. In the acute eye irritation study, Aller-7 was found to have minimal irritancy to eyes of rabbits. In the repeated-dose 90-day oral toxicity study, Aller-7 was administered at dose levels of 100, 300, and 1,000 mg/kg rat body weight for 90 consecutive days by oral gavage. Aller-7 did not induce any significant change in the hematological parameters. No ocular abnormalities were observed. Some minor histopathological changes were observed, but did not reveal any significant treatment-related histopathological changes. The above findings revealed that the no observed adverse effect level (NOAEL) of Aller-7 is greater than 1,000 mg/kg body weight. Taken together, these studies demonstrate the broad spectrum safety of Aller-7.