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Lymph Go

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Echinacea purpurea Extract

Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses

Abstract

Background: Several Echinacea species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF) of a stem and leaf (S+L) extract of E. purpurea ([BF/S+L/Ep]) containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs) were analyzed using primary cultures.

Results: Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs). Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (Cdh10, Itga6, Cdh1, Gja1 and Mmp8), or were chemokines (Cxcl2, Cxcl7) or signaling molecules (Nrxn1, Pkce and Acss1). TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. In vitro flow cytometry analysis of chemotaxis-related receptors and in vivo cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups.

Conclusion: Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical application of Echinacea or other candidate medicinal plants.

Source: Yin SY, Wang WH, Wang BX, Aravindaram K, Hwang PI, Wu HM, Yang NS. Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses. BMC Genomics. 2010 Nov 1;11:612. doi: 10.1186/1471-2164-11-612. PMID: 21040561; PMCID: PMC3091753.

Bromelain

Properties and Therapeutic Application of Bromelain: A Review

Abstract

Bromelain belongs to a group of protein digesting enzymes obtained commercially from the fruit or stem of pineapple. Fruit bromelain and stem bromelain are prepared differently and they contain different enzymatic composition. “Bromelain” refers usually to the “stem bromelain.” Bromelain is a mixture of different thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors. In vitro and in vivo studies demonstrate that bromelain exhibits various fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities. Bromelain is considerably absorbable in the body without losing its proteolytic activity and without producing any major side effects. Bromelain accounts for many therapeutic benefits like the treatment of angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics. It also relieves osteoarthritis, diarrhea, and various cardiovascular disorders. Bromelain also possesses some anticancerous activities and promotes apoptotic cell death. This paper reviews the important properties and therapeutic applications of bromelain, along with the possible mode of action.

Source: Pavan R, Jain S, Shraddha, Kumar A. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203. doi: 10.1155/2012/976203. Epub 2012 Dec 10. PMID: 23304525; PMCID: PMC3529416.

Bromelain, a Group of Pineapple Proteolytic Complex Enzymes (Ananas comosus) and Their Possible Therapeutic and Clinical Effects. A Summary

Abstract

Bromelain is a complex combination of multiple endopeptidases of thiol and other compounds derived from the pineapple fruit, stem and/or root. Fruit bromelain and stem bromelain are produced completely distinctly and comprise unique compounds of enzymes, and the descriptor “Bromelain” originally referred in actuality to stem bromelain. Due to the efficacy of oral administration in the body, as a safe phytotherapeutic medication, bromelain was commonly suited for patients due to lack of compromise in its peptidase efficacy and the absence of undesired side effects. Various in vivo and in vitro studies have shown that they are anti-edematous, anti-inflammatory, anti-cancerous, anti-thrombotic, fibrinolytic, and facilitate the death of apoptotic cells. The pharmacological properties of bromelain are, in part, related to its arachidonate cascade modulation, inhibition of platelet aggregation, such as interference with malignant cell growth; anti-inflammatory action; fibrinolytic activity; skin debridement properties, and reduction of the severe effects of SARS-Cov-2. In this paper, we concentrated primarily on the potential of bromelain’s important characteristics and meditative and therapeutic effects, along with the possible mechanism of action.

Source: Varilla C, Marcone M, Paiva L, Baptista J. Bromelain, a Group of Pineapple Proteolytic Complex Enzymes (Ananas comosus) and Their Possible Therapeutic and Clinical Effects. A Summary. Foods. 2021; 10(10):2249. https://doi.org/10.3390/foods10102249

Melilotus, Rutin and Bromelain in primary and secondary lymphedema

Abstract

As reported in the literature, benzopyrones (alpha and gamma) have important effects on the microcirculation through various mechanisms. Coumarins are an alpha-benzopyrone as derivatives of Melilotus Officinalis, while bioflavonoids are a gamma-benzopyrone and include Rutin. Alpha-benzopyrones have two fundamental pharmacological effects: they have pro-lymphokinetic action by activating contractility of lymphangions; and the activation of macrophages to provide a proteolytic effect. Gamma-benzopyrones, such as Rutin, have an important anti-exuding and membrane stabilizing effect. Bromelain is known for its anti-inflammatory effect. The present study enrolled 52 patients with primary and/or secondary lymphedema in clinical stages I or II (according to the ISL classification) with 31 cases involving the lower limbs and 21 cases involving the upper limbs. All subjects were given for six months a natural compound consisting of 100 mg of natural Melilotus, that contains 20 grams of Coumarin, 300 mg of Rutin and 100 mg of Bromelain. The following parameters were studied at zero time (T0), after three months (T1), and after six months of treatment (T2): pitting, Stemmer's sign, measurement of limb circumferences, measurement of superficial tissue thickness in the affected limbs using ultrasound, and blood tests to evaluate hepatic function (ALT, AST, GGT, total and fractional bilirubin). At the end of the treatment (T2), the following results were observed: disappearance of pitting in 72% of the cases; unchanged Stemmer's sign; average decrease in limb circumferences of 4.2 cm; and average reduction of the superficial thickness of 29%. There was no variation in the liver function parameters examined. The combination of natural compounds (Melilotus, Rutin, and Bromelain) has been shown to be a valuable aid in the clinical control of both primary and secondary lymphedema of clinical stages I and II as well as in control of inflammatory phenomena related to chronic stasis. There were no side effects and no alteration of liver function parameters found.

Source: Michelini S, Fiorentino A, Cardone M. Melilotus, Rutin and Bromelain in primary and secondary lymphedema. Lymphology. 2019;52(4):177-186. PMID: 32171184.

Dandelion Extract (leaf)

The diuretic effect in human subjects of an extract of Taraxacum officinale folium over a single day

Abstract

Background: Taraxacum officinale (L.) Weber (Asteraceae) has been extensively employed as a diuretic in traditional folk medicine and in modern phytotherapy in Europe, Asia, and the Americas without prior clinical trial substantiation.

Objectives: In this pilot study, a high-quality fresh leaf hydroethanolic extract of the medicinal plant T. officinale (dandelion) was ingested by volunteers to investigate whether an increased urinary frequency and volume would result.

Design: Volume of urinary output and fluid intake were recorded by subjects. Baseline values for urinary frequency and excretion ratio (urination volume:fluid intake) were established 2 days prior to dandelion dosing (8 mL TID) and monitored throughout a 1-day dosing period and 24 hours postdosing.

Results: For the entire population (n = 17) there was a significant (p < 0.05) increase in the frequency of urination in the 5-hour period after the first dose. There was also a significant (p < 0.001) increase in the excretion ratio in the 5-hour period after the second dose of extract. The third dose failed to change any of the measured parameters.

Conclusions: Based on these first human data, T. officinale ethanolic extract shows promise as a diuretic in humans. Further studies are needed to establish the value of this herb for induction of diuresis in human subjects.

Source: Clare BA, Conroy RS, Spelman K. The diuretic effect in human subjects of an extract of Taraxacum officinale folium over a single day. J Altern Complement Med. 2009 Aug;15(8):929-34. doi: 10.1089/acm.2008.0152. PMID: 19678785; PMCID: PMC3155102.

Lemon Peel Powder (peel)

Herbs as old potential treatments for lymphedema management: A systematic review

Abstract

Introduction: Herbs have been reported to be effective in reducing lymphedema burden. This paper aimed to review literature reporting on herbs for lymphedema treatment.

Methods: A systematic review was performed using the PRISMA guideline. Clinical studies on herbal intervention and lymphedema were included. Evidence on the effectiveness of herbal interventions for desired outcomes including reduction of edema volume, other symptoms, quality of life and inflammation were collected and assessed in detail.

Results: In all twenty studies were included in this review. Of these 14 studies were randomized clinical trials and the rest were prospective pilot studies. Herbal treatment was reported for breast cancer-related lymphedema in most studies and coumarin was the most reported herb that used for lymphedema management. Edema volume reduction (17 out of 20) and symptoms improvement (15 out of 20) were the outcomes reported in most studies.

Conclusion: Phytochemicals can be a promising pharmacotherapy for lymphedema management. However, further evidence is needed to establish definite effectiveness for the use of herbal remedies for lymphedema management.

Source: Casley-Smith, J. R., Morgan, R. G., & Piller, N. B. (1993). Treatment of Lymphedema of the Arms and Legs with 5,6-Benzo-[alpha]-pyrone. New England Journal of Medicine, 329(16), 1158–1163. doi:10.1056/nejm199310143291604.

Cleavers (Galium aparine)

Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L.

Abstract

Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus. The herb of G. aparine is part of folk remedies and dietary supplements. In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol. The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols were determined spectrophotometrically, with extractives and polysaccharides quantified gravimetrically. The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation. Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside. Significantly, quercetin 3-O-rhamnoglucoside-7-O-glucoside was first isolated and identified in Galium species so far investigated. All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active. The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.

Source: Ilina T, Kashpur N, Granica S, Bazylko A, Shinkovenko I, Kovalyova A, Goryacha O, Koshovyi O. Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Plants (Basel). 2019 Nov 25;8(12):541. doi: 10.3390/plants8120541. PMID: 31775336; PMCID: PMC6963662.

Burdock Powder (root)

Effects of aquarobic exercise and burdock intake on serum blood lipids and vascular elasticity in Korean elderly women

Abstract

Background: The elderly's health issues are often complex and tend to lead to chronic diseases; such issues can be due to a fitness decline resulting from a lack of physical activities. The burdock root is a blood purifier, lymphatic system strengthener, and natural diuretic. The purpose of this study was to analyze the effects of aquarobic exercise and burdock intake on serum blood lipids and vascular elasticity in elderly women by implementing a 12-week program with these interventions.

Methods: Forty elderly female volunteer subjects aged 70 to 80years comprised the control group (n=8), aquarobic exercise group (n=11), aquarobic exercise and burdock intake combination group (n=11), and burdock intake group (n=10). The variables of serum blood lipids, and vascular elasticity were measured in all participants before and after the 12-week study.

Results: Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels significantly decreased in the aquarobic exercise group and aquarobic exercise and burdock intake combination group (p<0.05, p<0.01, p<0.001). No statistically significant changes in pulse wave velocity were also found within or between the groups before and after participation in the 12-week program.

Conclusions: Our findings indicate that aquarobic exercise and burdock intake improved the serum blood lipid levels and vascular elasticity of Korean elderly women. Additionally, burdock extract intake may be useful in vascular health by playing a secondary role in disease prevention and health promotion.

Source: Ha MS, Kim JH, Kim YS, Kim DY. Effects of aquarobic exercise and burdock intake on serum blood lipids and vascular elasticity in Korean elderly women. Exp Gerontol. 2018 Jan;101:63-68. doi: 10.1016/j.exger.2017.11.005. Epub 2017 Nov 14. PMID: 29154814.

Kelp Extract (Laminaria japopnica)(std. to 10% fucoxanthin)

Anticancer Effects of Fucoxanthin through Cell Cycle Arrest, Apoptosis Induction, Angiogenesis Inhibition, and Autophagy Modulation

Abstract

Cancer accounts for one in seven deaths worldwide and is the second leading cause of death in the United States, after heart disease. One of the standard cancer treatments is chemotherapy which sometimes can lead to chemoresistance and treatment failure. Therefore, there is a great need for novel therapeutic approaches to treat these patients. Novel natural products have exhibited anticancer effects that may be beneficial in treating many kinds of cancer, having fewer side effects, low toxicity, and affordability. Numerous marine natural compounds have been found to inhibit molecular events and signaling pathways associated with various stages of cancer development. Fucoxanthin is a well-known marine carotenoid of the xanthophyll family with bioactive compounds. It is profusely found in brown seaweeds, providing more than 10% of the total creation of natural carotenoids. Fucoxanthin is found in edible brown seaweed macroalgae such as Undaria pinnatifida, Laminaria japonica, and Eisenia bicyclis. Many of fucoxanthin’s pharmacological properties include antioxidant, anti-tumor, anti-inflammatory, antiobesity, anticancer, and antihypertensive effects. Fucoxanthin inhibits many cancer cell lines’ proliferation, angiogenesis, migration, invasion, and metastasis. In addition, it modulates miRNA and induces cell cycle growth arrest, apoptosis, and autophagy. Moreover, the literature shows fucoxanthin’s ability to inhibit cytokines and growth factors such as TNF-α and VEGF, which stimulates the activation of downstream signaling pathways such as PI3K/Akt autophagy, and pathways of apoptosis. This review highlights the different critical mechanisms by which fucoxanthin inhibits diverse cancer types, such as breast, prostate, gastric, lung, and bladder development and progression. Moreover, this article reviews the existing literature and provides critical supportive evidence for fucoxanthin’s possible therapeutic use in cancer.

Source: Ahmed SA, Mendonca P, Elhag R, Soliman KFA. Anticancer Effects of Fucoxanthin through Cell Cycle Arrest, Apoptosis Induction, Angiogenesis Inhibition, and Autophagy Modulation. Int J Mol Sci. 2022 Dec 17;23(24):16091. doi: 10.3390/ijms232416091. PMID: 36555740; PMCID: PMC9785196.

Rutin (Sophora japonica)(whole flower bud)

Melilotus, Rutin and Bromelain in primary and secondary lymphedema

Abstract

As reported in the literature, benzopyrones (alpha and gamma) have important effects on the microcirculation through various mechanisms. Coumarins are an alpha-benzopyrone as derivatives of Melilotus Officinalis, while bioflavonoids are a gamma-benzopyrone and include Rutin. Alpha-benzopyrones have two fundamental pharmacological effects: they have pro-lymphokinetic action by activating contractility of lymphangions; and the activation of macrophages to provide a proteolytic effect. Gamma-benzopyrones, such as Rutin, have an important anti-exuding and membrane stabilizing effect. Bromelain is known for its anti-inflammatory effect. The present study enrolled 52 patients with primary and/or secondary lymphedema in clinical stages I or II (according to the ISL classification) with 31 cases involving the lower limbs and 21 cases involving the upper limbs. All subjects were given for six months a natural compound consisting of 100 mg of natural Melilotus, that contains 20 grams of Coumarin, 300 mg of Rutin and 100 mg of Bromelain. The following parameters were studied at zero time (T0), after three months (T1), and after six months of treatment (T2): pitting, Stemmer's sign, measurement of limb circumferences, measurement of superficial tissue thickness in the affected limbs using ultrasound, and blood tests to evaluate hepatic function (ALT, AST, GGT, total and fractional bilirubin). At the end of the treatment (T2), the following results were observed: disappearance of pitting in 72% of the cases; unchanged Stemmer's sign; average decrease in limb circumferences of 4.2 cm; and average reduction of the superficial thickness of 29%. There was no variation in the liver function parameters examined. The combination of natural compounds (Melilotus, Rutin, and Bromelain) has been shown to be a valuable aid in the clinical control of both primary and secondary lymphedema of clinical stages I and II as well as in control of inflammatory phenomena related to chronic stasis. There were no side effects and no alteration of liver function parameters found.

Source: Michelini S, Fiorentino A, Cardone M. Melilotus, Rutin and Bromelain in primary and secondary lymphedema. Lymphology. 2019;52(4):177-186. PMID: 32171184.

References:
  1. https://pubmed.ncbi.nlm.nih.gov/21040561/
  2. https://pubmed.ncbi.nlm.nih.gov/23304525/
  3. https://www.mdpi.com/2075-1729/14/4/483
  4. https://www.mdpi.com/2304-8158/10/10/2249
  5. https://pubmed.ncbi.nlm.nih.gov/32171184/#:~:text=The%20combination%20of%20natural%20compounds,phenomena%20related%20to%20chronic%20stasis.
  6. https://pubmed.ncbi.nlm.nih.gov/19678785/
  7. https://pubmed.ncbi.nlm.nih.gov/33221590/
  8. https://pubmed.ncbi.nlm.nih.gov/31775336/
  9. https://pubmed.ncbi.nlm.nih.gov/29154814/#:~:text=The%20burdock%20root%20is%20a,week%20program%20with%20these%20interventions.
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785196/
  11. https://pubmed.ncbi.nlm.nih.gov/32171184/