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Taxon confusion
Physalis, a genus of the family Solanaceae consists of about 100 species. Among these, Physalis minima (pantug-pantugan) has been confused with P. angulata. Some compilations list them as synonyms, as other list them as separate species. In Bangladesh, the two have long been misidentified. A critical examination separates them as species. (See below: sources)
Botany
Putokan is an erect and branching herb with angled and much branched
stems, growing to 1 meter high. Petioles are 1 to 5 centimeters long. Leaves are alternate,
oblong-ovate, up to 9 centimeters long with pointed tips and acute and unequal
base with margins that are more or less entire. Flowers are solitary,
campanulate, pale yellow, up to 6 millimeters long. Fruit is a berry, 1.5 to
2 centimeters diameter surrounded by an inflated and ovoid calyx.
Distribution
- Native to tropical America.
- Introduced to the Philippines during the Spanish times, now widely distributed.
- Propagated by seeds.
Constituents
- Methanol extract of fruits yielded alkaloids, saponins, phenols, etc.
- Phytochemical screening yielded steroids, flavonoids, and alkaloids.
- Screening of various crude extracts for secondary metabolites yielded alkaloids, tannins, terpenoids, phenolics, and terpenoids. (see study below) (27)
- Hydrodistillation of leaves for essential oil yielded
main chemical classes of diterpenes (31.7%), fatty acids (22.8%), oxygenated sesquiterpenes (22.3%), and aromatic compounds (13.6%). with trace amounts of monoterpene compounds. Major constituents were: phytol (31.7%) and hexahydrofarnesyl acetone (18.8%), with significant amounts of nonadecane (8.6%) and n-hexadecanoic acid (5.0%). (41)
- Study of n-butanol fraction from aqueous of extracts of dried leaves isolated three flavonoids, viz., quercetin, quercetin 3-O-methyl ester, and isoquercetin. (43)
- Study of stems and leaves isolated five new physalins, i.e., physalin V, a novel 1,10-seco one (1), physalin VIII (5), physalin IX, and two new ones, physalins VI and VII, along with eleven known analogues
(3 and 7-16). (see study below) (46)
- Study of whole plant yielded four phenolic glycosides, i.e., methyl salicylate 2-O-triglycoside
(1), icariside E5 (2), quercetin 3-O-rutinoside (3), and isorhamnetin 3-O-rutinoside (4). (see study below) (49)
- Bioassay guided fractionation of whole plant identified two new withanolides (1-2) and six known analogues viz., physagulin F, physagulin K, physalin B, physalin F, physalin H, and 5-a-ethoxy-6ß-hydroxy-5-6-dihydrophysalin B. (see study below)
(51)
-Bioassay-guided fractionation of whole plant of P. angulata isolated a novel physalin, 25-hydroxylisophysalin B (1) along with three megastigmane glucosides (2-4) and eight known physalins (5-12) (see study below)
(57)
Properties
- Phytochemical studies yield plant
steroids Physalins with activity against numerous type of human and
animal cancer cells.
- Studies have shown anti-inflammatory, genotoxic,
antimicrobial, anti-leishmanial, immunomodulatory, molluscicidal, anticancer, antidiabetic, anti-asthmatic properties.
Parts
utilized
Whole plant, leaves, roots.
 Uses
Edibility
- Fruits are edible, sweet-tart..
- Roots and epigeal parts used for tea or infusion.
-
Folkloric
- No reported folkloric medicinal
use in the Philippines.
- In the Amazon, leaf infusion used as diuretic.
- In Colombia, some tribes consider the fruits and leaves to be narcotic:
decoction of leaves used as anti-inflammatory and skin disinfectant.
- In the Amazon, leaf juice
used for worms.
- In the Solomon Islands,
a decoction of fruit used for infertility.
- In the West Indies and
Jamaica, leaves used to
prevent miscarriages.
- In Peru, leaf infusion
used for postpartum infections.
- In Peru and Brazil,
roots are sliced, macerated in rum, honeyed, and used for diabetes.
- In Brazil, used for asthma,
malaria, hepatitis, dermatitis and rheumatism.
Abortifacient
• In Cameroon, Physalis angulata is used in herbal
recipes for pregnancy termination. A dangerous practice uses dried and ground seeds which
are wet with saliva and rolled into a ball and inserted
into the vagina with expected fetal expulsion in a week. However, it
is commonly accompanied by abdominal pains, severe bleeding, anemia,
and sometimes, death.
Studies
• Anti-inflammatory:
Study showed inhibitory effects against acute and subacute inflammation
and significant inhibition of type IV allergic reaction in mice. (2)
• Genotoxicity:
Study evaluated the in vitro genotoxic effects of aqueous extracts of P. angulata using comet assay and micronucleus assay in human lymphocytes from 6 healthy donors. Results showed that although the Physalis extract was not cytotoxic, it
exhibited important genotoxic effects on human lymphocytes in vitro,
suggesting caution with its use. (3)
• Antimicrobial / Physalin B:
Study yielded complex physalin metabolites from the fruit capsules.
A mixture of physalins B, D, F, and G inhibited S aureus and Neisseria
gonorrhea. Physalin B by agar diffusion inhibited S. aureus by 85% and
may be considered responsible for the antimicrobial activity. (4)
• Antileishmanial / Physalins:
Physalins B and F were able to reduce the percentage of Leishmania-infected
macrophages and the intracellular parasite number in vitro without no
cytotoxicity to macrophages. Physalin F significantly reduced the lesion
size, parasite load, and histological alterations in Leishmania infected
mice. (6)
• Lipid Benefits / HDL Elevation:
Study showed that the flower extract of Physalis angulata in rats showed
a significant elevation of HDL-cholesterol. (7)
• Molluscicidal / Leaves and Roots:
Study showed the ethanolic extracts from the leaves and roots of Physalis
angulata are mollusicidal; while the ethanol extracts from the stem
and whole plant was inactive. (8)
• Immunomodulatory Effects:
Study investigated different extract fractions of Physalis angulata (PA-VII, PA-VII-A , PA-VII-B, PA-VII-C) for immunomodulatory effects in mice. PA-VII and PA-VII-C exhibited a strongly enhanced blastogenesis response, together with a stimulatory
activity on B cells (less on T cells). PA-VII, PA-VII-B and PA-VII-C caused augmentation of antibody responses. (9)
• Anticancer / Breast Cancer Cycle Arrest: Study showed Physalis angulata inhibited cell proliferation and induced
G2/M arrest and apoptosis in human breast cancer MAD-MB 231 and MCF-7
cells lines. (10)
• Anti-Neoplastic / Fruit Capsule: Study on its anti-neoplastic activity showed the most
significant inhibition from the fruit capsule fractions. The extract
of roots of PA is most often used for human hepatic disorders, but the
substance responsible for efficacy is still undefined. Physalin F has
shown antitumor activity against five human cancer lines, the most potent,
anti-hepatoma H A 22 T. (11)
• Antimicrobial / Essential Oil / Aerial and Root Parts: Study showed the essential oil extract to have both antifungal and antibacterial properties, with more of the former. The activities are more concentrated in the aerial parts of the plant. (15)
• Genotoxic Effects on in-vitro Human Lymphocytes: Study evaluated the in vitro genotoxic effects of an aqueous extract in human lymphocytes from 6 healthy donors. Results demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro. Although the extract did not show cytotoxicity, the in vitro genotoxic effects requires caution since in vivo genotoxicity has not been evaluated. (16)
• Physangulidine A / Withanolide / Apoptosis in Prostate Cancer Cells: Study evaluated the biologic effects of physangulidine A, one of three withanolides isolated in the study (physangulidines A-C). Physangulidine A significantly reduced of two hormone-independent prostate cancer cell lines. Results showed antimitotic and proapoptotic effects. (17)
• Antibacterial / Anti-Staphylococcal Activity / Fruit: Study evaluated the inhibitory effect of zinc oxide ointment formulation and unformulated crude extract of fruits of Physalis angulata against clinical wound isolates of Staphylococcus aureus and Pseudomonas aeruginosa. Results showed significant inhibitory activity against S. aureus suggesting efficacy in treating staphylococcal infections. (18)
• Anti-Ulcer / Leaves: Study evaluated the antiulcer effect of ethanolic extract of P. angulata leaves in different models of gastric ulceration in rats. Results showed a protective effect which might be mediated by anti-secretory and cytoprotective mechanisms. (19)
• Topical Anti-Inflammatory / Physalin E / Experimental Dermatitis: Study evaluated the anti-inflammatory effect of physalin E, a seco-steroid isolated from P. angulata on acute and chronic models of dermatitis induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and oxazolone in mouse ear. Topically applied physalin E potently inhibited the induced dermatitis, with reversal of effects by mifepristone, a steroid antagonist. (20)
• Anti-Diabetic / Fruit Extracts: Study evaluated the in vitro antidiabetic activity of P. angulata fruit extracts. The methanol extract showed inhibition showed prominent antidiabetic properties in vitro with inhibition of alpha amylase and alpha glucosidase. (21)
• Inhibition of Tumor Metastasis and Angiogenesis: Study of ethyl acetate extracts of P. angulata against human oral squamous carcinoma (HSC-3) and human umbilical vein endothelial cells showed anti-metastatic and anti-angiogenic activity, with a potential for development of chemopreventive agent for cancer and inflammation. (22)
• Anti-Inflammatory / Anti-Arthritic / Leaves: Study of various extracts and fractions of leaves showed in vitro anti-inflammatory activity by HRBC membrane stabilization method and in vitro activity by protein denaturation method. All extracts showed positive response compared to standard Diclofenac sodium. (23)
• Anti-Diabetic / Lipid Benefits / Roots: Study evaluated the antidiabetic potential of ethanolic root extract in alloxan induced diabetic rats. Results showed significant reduction of blood glucose, cholesterol, triglycerides and LDL, with significantly increase in HDL. (24)
• Anthelmintic / Larvicidal Leaves: A crude ethanolic leaf extract of P. angulata s0owed anthelmintic activity against Pheretima posthuma. A crude ethanolic extract sowed larvicidal activity against Culex quinquefasciatus species of mosquito larvae. (25)
• Anti-Asthmatic / Roots: Study evaluated the anti-asthmatic activity of an alcoholic extract of roots in ovalbumin induced experimental mice model. Results showed inhibition of ovalbumin induced asthma by decreasing the release of inflammatory mediators. The activity was probably through reduction of inflammatory mediator's release. (•)
• Antibacterial: Antimicrobial screening of ethanolic extract of plant at different concentrations of 25, 50, 100, and 125 mg/ml revealed various zones of inhibition from 8.2 to 17.2 mm for different organisms. (see constituents above) (27)
• Anthelmintic / Larvicidal / Leaves: Study evaluated rude ethanolic leaf extract of P. angulata for anthelmintic activity against Pheretima posthuma and mosquito larvicidal activity against Culex quinquefasciatus. Results showed significant paralysis and death of helminthes especially at higher concentration of 50 mg/ml, compared to standard piperazine citrate. Larvicidal activity was observed with LC50 value of 51.8802 mg/l. (28)
• Antidiabetic / Fruit: Study evaluated the antidiabetic effect of an isolated compound from P. angulata in alloxan induced diabetic rats. The isolated compound significantly (p<0.05) reduced blood sugar level. Glibenclamide 150 mg/kg p.o. was used as reference drug. (29)
• Anti-Inflammatory / Roots: Study evaluated a lyophilized aqueous extract from roots of Physalis angulata for anti-inflammatory effect on inflammation induced by injection of 1% carrageen-an into subcutaneous rat's air pouches. Results showed powerful anti-inflammatory and immunomodulatory activities, interfering with the cyclooxygenase pathway, lymphocyte proliferation, NO, and TGF-ß production. (30)
• Physalins / Antinociceptive / Roots: Study evaluated the antinociceptive properties of physalins B, D, F, and G isolated from P. angulata in inflammatory and centrally mediated pain tests in mice. Results showed Physalins B, D, F, and G has antinociceptive properties associated with central, but not anti-inflammatory, events. (31)
• Cytotoxicity / COX-2 Inhibition in MCF-7 Cells: Ceplukan (P. angulata) have shown cytotoxic effects towards various cancer cell lines: HeLa, KB, Colo 205, Calu and MCF-7 cells in vitro. One of the mechanisms of cytotoxicity is the inhibition of cyclooxygenase-2 (COX-2) pathway. Study of a 70% ethanol extract of P. angulata showed inhibitory effect on COX-2 activity in MCF-7 cell with IC50 of 37.57 ± 3.11 µg/mL. (32)
• Anti-Leishmaniasis / Roots: Study evaluated an aqueous extract of roots of P. angulata on Leishmania proliferation, morphology, and the presence and contribution of physalins to its pharmacologic efficacy. Physalins A, B, C, D, E, F, G, and H were isolated from the roots. Results showed AEPa effectively promotes antileishmanial activity with several important morphological alterations, with no cytotoxic effects on host cells. (33)
• Physagulin-F / Anti-Diabetic / Fruit: Study isolated physagulin-F from Physalis angulata fruit. The compound was evaluated for anti-diabetic activity against STZ-induced diabetic rats. The compound produced significant (p<0.5) reduction in blood glucose level, similar to the blood glucose reduction (p<0.5) produced by standard drug, glibenclamide. (34)
• Intestinal Anti-Inflammatory Activity: Study e valuated the effects of P. angulata extract in a TNBS (trinitrobenzenesulphonic acid) model of rat intestinal inflammation. The standardized supercritical CO2 extract promoted significant reduction in MPO and ALP activities, reducing oxidative stress and neutrophil infiltration. Results conclude that the PA extract is an intestinal anti-inflammatory product that modulates oxidative stress, immune response and expression of inflammatory mediators and has potential in the treatment of inflammatory bowel disease. (35)
• Anti-Asthmatic / Leaves: Study evaluated a methanolic extract of leaves of P. angulata for anti-histaminic activity using isolated animal smooth muscle models. Results showed inhibitory activity in guinea pig ileum preparation, guinea pig tracheal chain preparation and rat fundus strip preparation. Results suggest a potential source of an herbal drug with less side effects, less cost, and effective option for the treatment of asthma. (36)
• Analgesic / Anti-Inflammatory
/ Leaves: Study evaluated the analgesic and anti-inflammatory activity of methanolic leaf extract of Physalis angulata using acetic acid-induced abdominal contraction or writhing analgesic models in Swiss albino mice. The plant extract showed dose-dependent analgesic and anti-inflammatory effect. (37)
• Cytotoxic Withanolides
/ Cytotoxicity Against Cancer Cell Lines / Aerial Parts: Study isolated a new withanolide, Physaguilide P, together with five known withanolides (2-6) from the aerial parts of P. angulata. Compound 1 showed significant cytotoxicities against human osteosarcoma cell line MG-63, HepG-2 hepatoma cells and breast cancer cells MDA-MB-231 with IC50s of 3.50, 4.22, and 15.74 µM, respectively. (38)
• Antinociceptive / Roots: Study evaluated the antinociceptive effect of aqueous extract of roots of P. angulata. Results showed marked antinociception against acetic acid-induced visceral pain and inflammatory pain responses induced by formalin in mice. (39)
• Non-Mutagenic Therapy to Food Borne Illnesses: Study evaluated the potential of P. angulata as an herbal oral ProVac for infectious diseases caused by food borne pathogens. Fractionated extracts showed the presence of alkaloids, terpenoids, cardiac glycosides and sterols that inhibited the growth of Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. The extracts showed no mutagenic effect against S. typhimurium TA 98. The partially purified herbal extract of PA showed antimicrobial activity against all food pathogens tested. (40)
• Physalin B / NOXA-Related Apoptosis of Human Melanoma A375 Cells: Study investigated the anti-melanoma effect of physalin B. Physalin B exhibited cytotoxicity towards v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma A375 and A2058 cells with IC50 values lower than 4.6 µg/ml. Results suggest physalin B can induce apoptosis of melanoma cancer cells via the NOXA, caspase-3, and mitochondria-mediated pathways. Study suggests a potential as chemotherapeutic lead compound for the treatment of malignant melanoma. (42)
• Inhibitory Potential on Mycobacterium: Mycobacterium ulcerans disease is a serious threat for people living in rural remote areas. Study reports on a compilation of medicinal plants that demonstrated inhibitory potential on Mycobacterium ulcerans. A mixture of J. curcas, G. hirsutum, Physalis angulata, and D. regia inhibited the growth of 7 M. ulcerans isolates with MIC value of 6.25 to 25 µg/mL. The major constituents of medical important in P. angulata are physalins and withanolides. Its anti-inflammatory, antimycobacterial, antinociceptive, and antitumor activities together with its inhibitory effect on M. ulcerans support its traditional use for Buruli ulcer treatment. (44)
• Herbal Formulation Against Malaria / AM1: AM-1 is formulated from J. curcas, G. hirsutum, Physalis angulata, and D. regia. The herbal formulation was tested on patients with suspected malaria and evaluated for acute and chronic toxicity effects on Sprague Dawley rats. The AM-1 eliminated malaria parasites (Plasmodium falciparum and P. malariae) from the peripheral blood of patients with malaria. Furthermore, it did not show undesired effects in both patients and laboratory rats. (45)
• Physalins / Antiproliferative / Anti-Inflammatory / Stems and Leaves: Study of stems and leaves yielded five new physalins along with eleven known analogues. Compounds 9 and 10 showed antiproliferative activities against all tested human cancer cells with IC50 values of 0.24-3.17 µM. Compounds 1, 3, 4, 9, 10, 13, 14, and 16 exhibited inhibitory activities against NO production. (see constituents above) (46)
• Inhibition of COX-2
/ Cytotoxicity: One of the mechanisms of P. angulata cytotoxicity is its inhibition of Cyclooxygenase-2 (COX-2) pathway. Study a 70% ethanol extract of P. angulata for inhibitory activity on COX-2 in MCF-7 cell. The EE showed an inhibitory effect on COX-2 activity in MCF-7 cell with an IC50 of 37.57 ± 3.11 µg/mL. (47)
• Immunomodulatory / Differentiation of Bone Marrow Cells: Study on the immunomodulatory properties of P. angulata showed the extract promoted the differentiation of bone marrow cells, particularly macrophages, with a potential as an immunomodulating agent. (48)
• Antibacterial / Physagulin / Fruits: Study evaluated the susceptibility of five human pathogenic bacteria to physagulin isolated from the fruits of P. angulata. Results showed inhibitory activity against all bacteria tested which was found to increase with increase in concentration. Maximum zone of inhibition was observed at concentration of 500 µg/ml. S. aureus and E. coli showed greater susceptibility. (49)
• Hepatoprotective / Phenolic Glycosides: Study of methanolic extract of whole plant isolated four phenolic glycosides. Compound 3, quercetin 3-O-rutinoside, exhibited significant hepatoprotective activity with IC50 of 17.08 µg/mL. against hydrogen peroxide induced Balb/c mice hepatocytes damage. (see constituents above) (50)
• Cytotoxic Withanolides / Whole Herb: Study of whole plant yielded two new withanolides (1-2), together with six known analogues (3-8). The withanolides exhibited strong cytotoxic activities against A549 (human non-small cell lung cancer cell line), Hela (human cervical cancer cell line) and p388 (human leukemia cell line) cell lines. Compounds 1 and 2 induced typical apoptotic cell death in A549 cell line in a dose-dependent manner. (see constituents above) (51)
• Diuretic / Leaves: Study evaluated the diuretic activity of methanolic leaf extract of Physais angulata in rats. Furosemide was used as positive control. Results showed diuretic effect as evidenced by significantly increased urine volume, along with increased excretion of Na, K, and Cl- ions. (52)
• Physalin E / Anti-Inflammatory / Stem and Aerial Parts: Physalin E is a naturally occurring seco-steroid from stems and aerial parts of P. angulata. Study evaluated the anti-inflammatory effect of physalin-E on RAW 264.7 mouse macrophages stimulated by lipopolysaccharaide (LPS). Results showed physalin E significantly inhibited LPS-induced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression and secretion in a dose-dependent manner. Physlin E exerted anti-inflammatory activities in LPS-induced macrophages and can inhibit the production of inflammatory cytokines by targeting the NF-kB signaling pathway. (53)
• Physalin F / Antitumor / Whole Plant: An ethanol extract of whole plant yielded physalin F and physalin D. Physalin F from the fraction PAIV-2 showed cytotoxicity in vitro by DEA and MTT assays on 8 cancer cell lines, five human cancer cell lines: HA22T (hepatoma), HeLa (cervix uteri), KB (nasopharynx), Colo-205 (colon) and Calu-1 (lung), and three animal cancer cell lines, H1477 (melanoma), Hep2 (laryngeal) and 8401 (glioma). Physalin D also showed antitumor effect against P388 lymphocytic leukemia in mice. Physalin D showed no activity. (54)
• Styrene and Methionine / Anti-Inflammatory: LC-MS/MS study isolated active compounds: styrene and methionine. In-silico study showed styrene and methionine have potency as inhibitory for GRK. GRK modulates the NFkB and TNF-α signaling pathways in the development of inflammation. The binding of styrene and methionine to GRK receptors decrease inflammation through inhibition of pro-inflammatory factors. (55)
• Antimycobacterial Physalins: Study bioassayed crude extracts and fractions from aerial parts of Physalis angulata for antimycobacterial activity. Physalins B, F, and D from fraction A1-29-12 exhibited MIC of 32 µg/ml against Mycobacterium tuberculosis H37Rv strain. (56 )
• Novel Cytotoxic Physalin: Bioassay-guided fractionation of whole plant of P. angulata isolated a novel physalin, 25-hydroxylisophysalin B (1) along with three megastigmane glucosides (2-4) and eight known physalins (5-12) All of the compounds exhibited cytotoxic activities against MCF-7 human mammary cells and HepG2 human hepatoma cells. (57)
• Pro-Apoptotic / Anti-Proliferative / Retinoblastoma Cells / Leaves: Study evaluated the effects of P. angulata leaf extract on apoptotic and anti-proliferation of retinoblastoma cells. Results showed the leaf extract improved apoptosis and significantly reduced the number of living cells in retinoblastoma cells. Improved apoptosis and decreased number of living cells occurred at a dose of 100 µg/ml. (58)
• Alleviation of Skin Fibrosis / Potential as Adjuvant Treatment in Scleroderma: - Double-blind randomized trial evaluated the effect of ciplukan extract as adjuvant on scleroderma skin fibrosis in standard therapy, based on modified Rodnan skin scale (MRSS), inflammatory biomarkers, immunology, and serum fibrosis. Results showed the extract with dose 3 X s0 mg for 12 weeks as adjuvant on scleroderma standard therapy alleviated skin fibrosis significantly based on MRSS and P1NP levels. (59)
• Physalin B / Suppression of Inflammatory Response to LPS in RAW264.7 Cells: Study evaluated physalin B effects on RAW264.7 macrophages stimulated by LPS. Physalin B significantly inhibited the expression and secretion of TNF-a and IL-6 induced by LPS. Physalin B can suppressed the inflammatory response to LPS in macrophages by inhibiting the production of inflammatory cytokines via NF-kB signaling. (60)
• Acute and Sub-Chronic Toxicity Study in Combination of Extract and Methylprednisolone: Study evaluated the safety of combination of P angulata (Cecendet) extract) and methylprednisolone with a single dose in mice (acute toxicity) and repeated doe for 90 days in rats (subchronic toxicity). Results showed no effect in mice behavior in singe dose therapy up to 5000 mg/kw (LD50>5g/kbw). In sub-chronic toxicity study with 1 g/kbw for 90 days, there were no deaths, organ toxicity, and effects on blood chemistries, blood cell count and urinalysis. (61)
• Anti-Sickling / Leaves: Study investigated the anti-sickling properties of aqueous leaf extracts of Physalis angulata and Dennettia tripetala on homozygous sickle cell erythrocyte. Treatment showed a significant increase (p<0.05) in GSH and SOD, and a significant decrease in catalase activities. Osmotic fragility testing showed an increase in membrane stability. Results showed both plants have antisickling potential and may be used for therapeutic management of sickle cell anemia. (62)
Availability
- Wild-crafted.
- Mullaca powder and tinctures in the cybermarket. |
