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Soapwort

Scientific Name(s): Saponaria officinalis L.
Common Name(s): Bouncing bet, Bruisewort, Dog cloves, Fuller's herb, Lady's-washbowl, Latherwort, Old-maid's-pink

Clinical Overview

Use

Soapwort is generally used to make natural soaps and in brightening and cleaning delicate fabrics. It has also been traditionally used to treat cough and bronchitis. Saponins and saporin have been conjugated with monoclonal antibodies (ie, rituximab) and growth factors to be used as targeted antitumor toxin and antiviral therapy; however, clinical trials are lacking to support these uses.

Dosing

Clinical evidence is lacking to support specific dosing recommendations. Bronchitis and cough: Doses of 1 to 2 g daily of soapwort extract or 1.5 g daily of the root have been traditionally used. Cancer: In early phase 1/2 clinical trials (1992 to 1996) using saporin-S6 immunotoxin conjugates, saporin-S6 was administered at a dose of 0.2 mg/kg in 1 or 2 weekly doses intravenously in patients with advanced Hodgkin disease or weekly infusions of 1 to 4 mg/dose (for a total of 5 to 20 mg) in patients with B-cell lymphoma.

Contraindications

Women with vaginal infections should not use soaps or cleansing products made with soapwort. See Toxicology.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Severe vomiting and diarrhea may occur if soapwort is ingested. In early clinical trials of saporin-S6–containing immunotoxins for antitumor targeted toxin therapy, mild transient adverse reactions, including fever, myalgia, transient increases in transaminases, weakness, thrombocytopenia, and vascular leak syndrome, occurred.

Toxicology

No data.

Botany

Soapwort is commonly found in pastures and along roadsides throughout Europe. It is a perennial, herbaceous plant that grows to between 30 and 60 cm in height, with a single smooth stem and lanceolate leaves. Its 5-petaled flowers appear from late July through September in fragrant clusters, varying from white to pale lavender in color.Meyer 1934

History

Soapwort is native to northern Europe and was introduced to England during the Middle Ages by Franciscan and Dominican monks who brought it as "a gift of God intended to keep them clean."Sculley 1989 By the end of the 16th century, use of the herb as a soap for washing dishes and laundry had become widespread in England. In 1957, botanist John Gerard recommended soapwort as a topical disinfectant for "green wounds" and "filthy diseases" in The Herball or Generall Historie of Plantes.Sculley 1989 Soapwort has been administered topically for the treatment of acne, psoriasis, eczema, and boils. An extract of the roots is a popular remedy for poison ivy. Soapwort extract and root have also been used to treat cough and bronchitis.Blumenthal 1998

Soapwort was probably first introduced to North America by the Puritans. Once established, the herb spread and now grows wild throughout the United States and southern Canada. The herb was used extensively in the early textile industry as a cleaning and sizing agent, a process known as "fulling" that accounts for the name "fuller's herb." The Pennsylvania Dutch used the herb to impart a foamy head to beer in brewing. To this day, some beer makers use saponins from the plant to provide and maintain a foamy head.Meyer 1934

Saporin, a type 1 ribosome-inactivating protein extracted from S. officinalis, is widely used as a toxin moiety in targeted antitumor toxins.Thakur 2013, Weng 2012 Saporin-S6 and other plant toxins in the ribosome-inactivating protein family have been isolated from S. officinalis L. seeds.Weng 2012 Preparation of the first saporin-S6–containing immunotoxin was completed in 1985, with the first phase 1/2 clinical trial conducted in 1992 in 4 patients with advanced refractory Hodgkin disease.Polito 2013

Chemistry

Soapwort contains water-soluble, steroidal saponins that form a soap-like lather. These active principles are found in all parts of the plantMeyer 1934 and act as surface active agents to facilitate cleaning. A number of the individual saponins have antiproliferative activity in cancer cells, which may be related to hemolytic effects.Lu 2015 Although phytoecdysteroids have been found in some species of the Caryophyllaceae family, they have not been identified in S. officinalis.Novozhilova 2015

The saponins isolated from S. officinalis have high detergent properties and are derived mostly from the sapogenins gypsogenic acid and hydroxygypsogenic acid.Gevrenova 2014 Saporin-S6 has been found to have 9 different isoforms isolated from the leaves, roots, and seeds of S. officinalis.Polito 2013 Saporin-L1, a leaf isoform, acts on numerous nucleic acid substrates (ie, herring sperm DNA, yeast tRNA, bacteriophage MS2 genomic RNA). Saporin, when conjugated with a cytokine or antibody-related ligand, is used as a targeted immunotoxin ("magic bullet"); saporin has also been found to be a potent inhibitor of HIV-1 integrase.Yadav 2015 The saporin conjugate is taken up by the target cell where cytotoxicity results from ribosome inactivation and subsequent protein inhibition.Brown 2013

In mice, soapwort saponins demonstrated a dose-dependent stimulation of both proinflammatory and antiinflammatory cytokines, including increased production of tumor necrosis factor-alpha.Kuznetsova 2014

Uses and Pharmacology

Antifungal activity

In vitro and animal data

Saponin-rich fractions extracted from Medicago sativa and S. officinalis were tested in vitro for activity against Candida albicans reference strain and 5 clinical strains for direct fungicidal and fungistatic activity. The extracts were tested alone as well as in combination with various antimycotics (eg, amphotericin B, miconazole, clotrimazole, ketoconazole, nystatin, natamycin, flucytosine). Although S. officinalis extract did not exhibit direct antifungal activity, it did exert strong germ tube formation inhibition and a potent synergy with caspofungin that almost completely inhibited biofilm formation. S. officinalis also demonstrated very high cytotoxicity when used at both high and low concentrations, making it a more likely candidate as an antifungal disinfectant than therapeutic agent; the high cytotoxicity of S. officinalis saponin-rich extract corresponded to its hemolytic activity.Sadowska 2014

Clinical data

Research reveals no clinical data regarding use of soapwort as an antifungal.

Anti-HIV activity

In vitro and animal data

Similar to many other type 1 ribosome-inhibiting proteins, saporin possesses potent anti-HIV integrase activity in vitro.Au 2000, Yadav 2015 The anti-HIV activity of saporin, as well as of 3 saporin mutants, was assayed to further define its anti-HIV mechanism of action. According to the results, saporin appears to enter cells via nonreceptor-mediated endocytosis and exhibits dose-dependent anti-HIV activity. The results also indicate that the anti-HIV activity of saporin is independent of its N-glycosidase activity; however, it appears to be associated with its apoptosis-inducing activity and in turn its cytotoxic activity.Yadav 2015

Clinical data

Research reveals no clinical data regarding use of soapwort as an anti-HIV agent.

Antitumor activity

Protein synthesis is inactivated by saporin through the irreversible removal of an essential adenine. Because the cytotoxicity of saporin alone is low, it is conjugated with specific targeting ligands (ie, monoclonal antibodies, growth factors) to direct the toxic potential of saporin to cancer cells that are overexpressing cancer-associated antigens. Combining saporin and the targeting ligand with another saponin augments the delivery of the antitumor toxin to the cancer cell cytosol.Weng 2012

Experimental and animal data

The antitumor effect of the immunotoxin saporin-S6-rituximab conjugate was assessed in CD20+ lymphoma cell lines; both a dimeric and monomeric conjugate were tested. Saporin-S6 showed increased cytotoxicity after conjugation with rituximab; the dimeric (high-molecular-weight immunotoxin) was more active than the monomeric.Bortolotti 2016 In another series of in vitro and in vivo studies based on previous results demonstrating that saporin fused with epidermal growth factor (Sap3-EGF) reduces tumor volume more than 94%, a highly purified single saponin extracted from the roots of S. officinalis (SO-1861) was combined with Sap3-EGF as a targeted toxin to determine cytotoxic efficacy. In vitro tests confirmed a 6,900-fold increase in cytotoxicity in a synergistic fashion. According to the acute toxicity studies in mice, the purified saponin was nontoxic up to a dose of 100 mcg per treatment. An acute dose of 200 mcg of the purified saponin (SO-1861) resulted in severe liver damage and was fatal in all mice by day 2, whereas no animals in the 100 mcg group died during the 28-day study period. The combination of SO-1861 30 mcg plus Sap3-EGF 0.1 mcg reduced the average tumor volume by more than 90% compared with placebo-treated mice. Additionally, 8 of 10 treated mice exhibited complete remission compared with 1 in 8 controls.Thakur 2013 Similar results have been reported using the purified triterpenoid saponin SO-1641 in combination with saporin-EGF in tumor-bearing mice.Weng 2012 Similar results were also observed when SO-1861 was combined with saporin-rituximab, which produced an approximate 700-fold increase in cytotoxicity in human B-cell Burkitt lymphoma cells.Gilabert-Oriol 2016 The use of the saponin SO-1861 with lipid-based and peptide nanocarriers for the efficient delivery of DNA and/or siRNA to cells has also been demonstrated in 3 different cell lines.Weng 2015

The crude extracts from 4 species of the Caryophyllaceae family, including S. officinalis, were tested for cytotoxic effects in rat and human macrophage cell lines. S. officinalis extract exhibited the most cytotoxic activity among the extracts tested in the rat alveolar macrophage cells and reduced cell viability by 60% (P<0.0001), but was less cytotoxic than Dianthus sylvestris extract in human monocytes. S. officinalis was 1 of 3 extracts to demonstrate time-dependent caspase-3 activation of apoptosis.Gevrenova 2014

Clinical data

In 1992, patients with advanced Hodgkin disease (n=16) were enrolled in the first phase 1/2 clinical trial testing a saporin-S6–containing immunotoxin. Saporin-S6 was conjugated with anti-CD30 Ber-H2 and administered intravenously at 0.2 mg/kg as saporin-S6 (0.8 mg/kg as immunotoxin) in 1 or 2 weekly doses. Overall, tumor mass was reduced in 60% of cases, with partial remission in approximately 42% of patients; responses lasted between 2 and 4 months. About 70% of patients experienced adverse reactions (eg, fever, myalgias, vascular leak syndrome, hepatotoxicity, thrombocytopenia). Weekly infusions containing escalating saporin-S6 doses ranging from 1 to 4 mg/dose (total of 5 to 20 mg) were used in 2 other early phase 1/2 trials in 1995 and 1996, with results varying from complete clearance of tumor in one patient with end-stage non-Hodgkin lymphoma to no response in a patient with end-stage chronic lymphocytic leukemia. When responses occurred, they were rapid but persisted for less than 28 days.Polito 2013

Bone cancer pain

Animal data

Bone cancer in companion dogs is an animal model of naturally occurring bone cancer that closely mirrors the disease and its progression in humans. In a single-blind, randomized controlled trial, the analgesic and functional efficacy of a single intrathecal dose of a substance P saporin (SP-SAP) conjugate immunotoxin that targets SP receptor–bearing neurons was evaluated in 70 companion dogs with appendicular bone cancer. SP-SAP was dosed at 20, 40, or 60 mcg for dogs weighing 10 to 15 kg, 16 to 30 kg, or more than 30 kg, respectively. Outcomes were measured at 2 weeks and monthly thereafter. Dogs in the control group that received standard of care therapy alone required additional intervention (ie, analgesics, euthanasia) significantly sooner than those in the SP-SAP treatment group (P=0.002). The number of dogs that required additional intervention was also significantly higher in the control versus treatment group (74% vs 24%, respectively; P=0.001). Pain scores and lameness were not significantly different between groups; pain scores were not significantly different from baseline.Brown 2013

Dosing

Clinical evidence is lacking to support specific dosing recommendations.

Bronchitis and cough

Doses of 1 to 2 g daily of soapwort extract or 1.5 g daily of the root have been traditionally used.Blumenthal 1998

Cancer

In early phase 1/2 clinical trials (1992 to 1996) using saporin-S6 immunotoxin conjugates, saporin-S6 was administered at a dose of 0.2 mg/kg in 1 or 2 weekly doses intravenously in patients with advanced Hodgkin disease or weekly infusions of 1 to 4 mg/dose (for a total of 5 to 20 mg) in patients with B-cell lymphoma.Polito 2013

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Few adverse effects have been reported with oral ingestion, except in cases of underlying disease of the mucosa (ie, ulcers). Severe vomiting and diarrhea may occur if soapwort is ingested.Dobelis 1986 In early phase 1/2 clinical trials, saporin-S6–containing immunotoxins produced mild transient adverse reactions, including fever, myalgia, transient increases in transaminases, weakness, thrombocytopenia, and vascular leak syndrome. Fever and myalgia, effects commonly reported with immunotoxins, were treated with steroid therapy.Polito 2013

Toxicology

None well documented. Women with vaginal infections should not use soaps or cleansing products made with soapwort; an in vitro study found increased growth of Trichomonas vaginalis in women treated with varying strengths of S. officinalis extracts.Hezarjaribi 2016

References

Au TK, Collins RA, Lam TL, Ng TB, Fong WP, Wan DC. The plant ribosome inactivating proteins luffin and saporin are potent inhibitors of HIV-1 integrase. FEBS Lett. 2000;471(2-3):169-172.10767416
Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; 1998:209-210.
Bortolotti M, Bolognesi A, Battelli MG, Polito L. High in vitro anti-tumor efficacy of dimeric rituximab/saporin-S6 immunotoxin. Toxins (Basel). 2016;8(6).27338475
Brown DC, Agnello K. Intrathecal substance P-saporin in the dog: efficacy in bone cancer pain. Anesthesiology. 2013;119(5):1178-1185.24195949
Dobelis IN, ed. Magic and Medicine of Plants. Pleasantville, NY: Reader's Digest Association; 1986:702.
Gevrenova R, Joubert O, Mandova T, Zaiou M, Chapleur Y, Henry M. Cytotoxic effects of four Caryophyllaceae species extracts on macrophage cell lines. Pharm Biol. 2014;52(7):919-925.24863282
Gilabert-Oriol R, Thakur M, Haussmann K, et al. Saponins from Saponaria officinalis L. augment the efficacy of a rituximab-immunotoxin. Planta Med. 2016;82(18):1525-1531.27392242
Hezarjaribi HZ, Momeni Z, Azadbakht M, Esboei BR, Fakhar M. Akbaria M. Effects of hydroalcoholic extract of Saponaria officinalis leaf on growth of Trichomonas vaginalis in vitro. J Mazandaran Univ Med Sci. 2016;25(134):52-59.
Kuznetsova TA, Ivanushko LA, Makarenkova ID, Cherevach EI, Ten’kovskaya LA. Effects of S. officinalis L. radix triterpene glycosides on innate immunity factors. Bull Exp Biol Med. 2014;156(3):366-369.
Lu Y, Van D, Deibert L, Bishop G, Balsevich J. Antiproliferative quillaic acid and gypsogenin saponins from Saponaria officinalis L. roots. Phytochemistry. 2015;113:108-120.25534953
Meyer JE. The Herbalist. Hammond, IN: Indiana Botanic Gardens, 1934.
Novozhilova E, Rybin V, Gorovoy P, Gavrilenko I, Doudkin R. Phytoecdysteroids of the East Asian Caryophyllaceae. Pharmacogn Mag. 2015;11(suppl 1):S225-S230.26109770
Polito L, Bortolotti M, Mercatelli D, Battelli MG, Bolognesi A. Saporin-S6: a useful tool in cancer therapy. Toxins (Basel). 2013;5(10):1698-1722.24105401
Sadowska B, Budzyńska A, Więckowska-Szakiel M, et al. New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans. J Med Microbiol. 2014;63(pt 8):1076-1086.24850879
Sculley FX. God's gift, nature's soap. Herb Q. 1989;(41):7.
Thakur M, Mergel K, Weng A, et al. Targeted tumor therapy by epidermal growth factor appended toxin and purified saponin: an evaluation of toxicity and therapeutic potential in syngeneic tumor bearing mice. Mol Oncol. 2013;7(3):475-483.23298730
Weng A, Manunta MD, Thakur M, et al. Improved intracellular delivery of peptide- and lipid-nanoplexes by natural glycosides. J Control Release. 2015;206:75-90.25758332
Weng A, Thakur M, von Mallinckrodt B, et al. Saponins modulate the intracellular trafficking of protein toxins. J Control Release. 2012;164(1):74-86.23063550
Yadav SK, Batra JK. Mechanism of anti-HIV activity of ribosome inactivating protein, saporin. Protein Pept Lett. 2015;22(6):497-503.25925771

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