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Malaysian Herbal Monograph
  • Written by Shahrul
  • Updated on December 18, 2024

Kadok Leaves

Piper sarmentosum Roxb.

Piperaceae

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Figure 1 : P. sarmentosum. (a) Plant habit; (b) leaves; (c) inflorescence; (d) inflorescence showing fruiting spike; (e) shoot with leaves and inflorescence. (Photos courtesy of Thiyagu, MARDI, 2014)

DEFINITION

Kadok leaves consist of the whole mature leaves of a vine of P. sarmentosum Roxb. (Piperaceae)

SYNONYM

Chavica sarmentosa (Roxb. ex Hunter) Miq.

VERNACULAR NAMES

Wild betel leaf (English) [ 1 ], chabai, kadok batu (Malay), jia ju, qing ju, xi ye qing wei teng (Chinese) [ 2 ].

CHARACTER

ColourFleshy green leaves and shoot system
OdourSlight pungent [ 3 , 4 ]
TasteDelicate [ 3 , 4 ]

IDENTIFICATION

Plant Morphology

Erect or ascending terrestrial, often stoloniferous, dioecious herb or shrublet and glabrous with long creeping procumbent fruit-bearing branches measuring 0.3-1.5 m tall with large, stout, sweet fruits on maturity [ 3 ]; most parts very finely powdery pubescent when young. Stems has thick cuticle, with scattered 1-2-celled non-glandular trichomes; swollen at nodes; short aerial. Leaves dark green, variable in shape and size, simple, alternate, heart shape, tender and cordate with 2-8 cm long petiole; lower leaves ovate-cordate, 7-15 cm x 5-14 cm, base cordate, apex cuminate, 5-7-veined; upper leaves oblong, ovate-oblong or obliquely oblong, 7-11 cm x 3-5 cm, ovate to obliquely or rounded at base, shortly acuminate at apex, 3-veined; primary veins 7, palmate, pair of veins usually arise 0.5-2 cm above from the base, prominently raised; cuticle thin, smooth; stomata rarely observed; glandular trichomes present mainly in the laminar region; non-glandular trichomes found on the veins; midrib prominently raised abaxially and slightly raised adaxially; trichomes mostly confined to the abaxial surface. Inflorescence an erect, axillary cylindrical spike, 1-2 cm long; spikeoblongoid, 2-5 cm long and 0.8-1 cm thick; peduncle as long as spike [ 5 , 6 ]. Flower unisexual ovary with either male or female flowers; 0.7 cm long; bracts circular, white, about 1 cm in diameter; stamens short; stigmas 3-4. Fruit an obovoid berry, 1.5 cm x 1 cm, connate to each other and adnate to bract but with free apex and sweet taste. Aerial roots are short, slender, cylindrical, brownish outgrowth from the lower nodes of stem.

Microscopy

Microscopic characters of P. sarmentosum leaves consist of fragments of epidermis cells and abaxial epidermis shows numerous anisocytic, anomocytic, actinocytic, tetracytic and cyclocytic stomata, with 3-7 subsidiary cells arranged in one or more whorls, measuring 24-30 µm long and 20-27 µm wide; adaxial epidermis consists of an outer epidermal layer having square or tangentially elongated rectangular shaped cells, measuring 14-40 µm high, 12-53 µm long, in surface view, stomata rarely observed; secretory cells 20-28 µm in diameter which are present in the mesophyll cells; fragments of spirally thickened vessel and simple unicellular trichome [ 7 ].

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Figure 2 : Microscopic characters of P. sarmentosum leaves powder. (a-b) Fragments of epidermis cells and stomata; (c) adaxial epidermis; (d) fragments of spirally thickened vessel; (e-f) simple unicell trichome. [Scale bars: a-d =20 µm; e =10 µm; f =5 µm]

Colour Tests

Observed colour of solution after treatment with various reagents:

HCl (conc.)Green
5% FeCl3Green

Thin Layer Chromatography (TLC)

Figure 3 : TLC profiles of beta-sitosterol (S), methanol extracts of P. sarmentosum dried leaves powder collected from different locations (L1-L3) observed under (a) UV at 254 nm and (b) UV at 366 nm before spraying and (c) visible light after spraying with anisaldehyde -sulphuric acid reagent.

Test Solutions Weigh about 1.0 g of P. sarmentosum dried leaves powder in a 50 mL screw-capped conical flask and add 25 mL methanol. Sonicate for 60 min at temperature 25°C and filter. Use the filtrate as test solution.
Standard solution Dissolve 5.0 mg of beta-sitosterol standard [CAS no.: 83-46-5] in 5 mL methanol to produce 1000 µg/mL stock solution. Dilute this stock solution in methanol to produce 500 µg/mL.
Stationary Phase HPTLC Silica gel 60 F254, 10 x 10 cm
Mobile phase Toluene : ethyl acetate; (5:1) (v/v)
Application
  1. Beta-sitosterol standard solution (S); 5 µL, as a band
  2. Methanol extracts of  P. sarmentosum dried leaves powder collected from different locations L1, L2 and L3 (5 µL, as bands)
Development distance 8 cm
Drying Air drying
Detection
  1. UV at 254 nm and
  2. UV at 366 nm before spraying and
  3. Visible light after spraying with anisaldehyde-sulphuric acid reagent and heat at 105°C for 3 min 

High Performance Liquid Chromatography (HPLC)

Test solution Extract about 5.0 g of the P. sarmentosum dried leaves powder with 10 mL of methanol. Sonicate the mixture for 60 min at temperature 25°C. Filter the mixture solution through a 0.45 µm syringe filter and inject the filtrate into the HPLC column.
Standard solution Dissolve 5.0 mg of beta-sitosterol standard [CAS no.: 83-46-5] in 5 mL methanol to produce 1000 µg/mL stock solution. Dilute this stock solution in methanol to produce 500 µg/mL.
Chromatographic system

Detector: UV 210 nm
Column: C18  (5 µm, 4.6 mm I.D x 250 mm)
Column oven temperature: 40oC
Flow rate: 1.1 mL/min
Injection volume: 20 µL
Mobile Phase (gradient mode)

Run Time

(min)

A – Water
(%)

B – Methanol (%)

0

5

95

10

0

100

25

0

100

30

5

95
System suitability requirement

Perform at least five replicate injections of the standard solutions (500 µg/mL). The requirements of the system suitability parameters are as follow:

  1. Symmetry factor (As) is not more than 1.5.
  2. Percentage of relative standard deviation (RSD) of the retention time (t r) for beta-sitosterol is not more than 2.0%.
Acceptance criteria
  1. Retention time (t r) of beta-sitosterol in the test solution is similar to the t r of the standard solution.
  2. The ultraviolet (UV) spectrum of beta-sitosterol in the test solution is similar to the UV spectrum of beta-sitosterol in the standard solution (optional supportive data).
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Figure 4 : HPLC chromatogram beta-sitosterol standard solution (500 µg/mL) at t r = 17.767 min.

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Figure 5 : HPLC full chromatogram of methanol extract of P. sarmentosum dried leaves showing peak corresponding to beta-sitosterol (t r = 17.609 min).

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Figure 6 : HPLC zoom chromatogram of methanol extract of P. sarmentosum dried leaves showing peak corresponding to beta-sitosterol (t r = 17.609 min).

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Figure 7 : UV spectrum of beta-sitosterol standard solution (500 µg/mL) and methanol extract of P. sarmentosum dried leaves.

PURITY TESTS

Foreign Matter
Not more than 2%
Ash Contents
Total ash Not more than 15%
Acid-insoluble ash Not more than 3%
Loss on Drying
Not more than 12%
Extractive Values
Water-soluble extracts
Hot method Not less than 22%
Cold method Not less than 15%
Ethanol-soluble extracts
Hot method Not less than 13%
Cold method Not less than 8%

SAFETY TESTS

Heavy Metals
Arsenic Not more than 5.0 mg/kg
Mercury Not more than 0.5 mg/kg
Lead Not more than 10.0 mg/kg
Cadmium Not more than 0.3 mg/kg
Microbial Limits
Total bacterial count Not more than 105 cfu/g
Total yeast and mould count Not more than 104 cfu/g
Bile-tolerant gram negative Not more than 104 cfu/g
Specific Pathogens
Salmonella spp. Absent in 25 g
Escherichia coli Absent in 1 g
Staphylococcus aureus Absent in 1 g
Pseudomonas aeruginosa Absent in 1 g

CHEMICAL CONSTITUENTS

Essential oil of the leaves has been found to contain monoterpenes (e.g. α-thujene, α-pinene, β-pinene, myrcene, limonene, trans-β-ocimene, linalool, 4-terpineol, α-terpineol, α-copaene, methyleugenol, β-elemene, α-phellandrene, eugenol and b-elemene), sesquiterpenes (e.g. α-cadinene, β-cadinene, cis-caryophyllene, trans-caryophyllene, germacrene-D, (-)-alloaromadendrene, α-humulene, germacrene B, δ-cadinene, caryophyllene oxide, myristicine, spathulenol, β-caryophyllene, α-farnesene, γ-cadinene, E,Z-farnesol and E,E-farnesol), a sesquiterpenoid (e.g. β-eudesmol) and others (e.g. methyl 3-phenylpropionate, safrole, tridecane, bicycloelemene, β-borbonene,  elemicine, eusarone, nerol, cis-asarone, cedarene, cadinol, trans-asarone, n-heptadecane, isobutyl phthalate, butyl phthalate, phytol, bis(2-ethylhexyl) phthalate, piperitone, cinnamyl alcohol, α-ionone, β-guaiene, ethyl laurate, bicylogermacrene, cadinadiene, guaiol, dehydrocarveol, t-muurolol, β-bisabolol, δ-cadinol and α-cadinol) [ 8 , 9 ].

Methanol extract of the leaves has been found to contain phenylpropanoyl amides (e.g. chaplupyrrolidone A, chaplupyrrolidone B and deacetylsarmentamide) [ 10 ].

MEDICINAL USES

Uses described in folk medicine, not supported by experimental or clinical data

Traditionally, a decoction of P. sarmentosum leaves is used as an embrocation (application by rubbing) to treat bone pain. The leaves are also used as poultice on the children’s heads for headache and as an embrocation for tinea [ 11 ].

Biological and pharmacological activities supported by experimental data

Antiplasmodial activity

Methanol (0.8 mg/mL) and chloroform (0.05 mg/mL) extracts of P. sarmentosum leaves caused 100% inhibition of Plasmodium falciparum after 48 hours of incubation [ 4 ].

Methanol extract of P. sarmentosum leaves (5 mg/kg/day) was administered intraperitoneally to Plasmodium berghei infected adult female ddY mice for four days. There is a lower parasitaemia (0.08-20.31%) in the treated group compared to control (0.16-31.17%) [ 4 ].

Antibacterial activity

Methanol extract of P. sarmentosum leaves inhibited the growth of Staphylococcus aureus (MIC 2000 µg/disc), Methicillin Resistant S. aureus (MRSA) (MIC 1000 µg/disc) and Pseudomonas aeruginosa (MIC 2000 µg/disc) using disk diffusion method [ 12 ].

Methanol extract of P. sarmentosum leaves (100 mg/disc) inhibited the growth of MRSA (inhibition zone = 10 mm) compared to distilled water (6 mm) using disk diffusion assay. The extract showed MIC value of 50 mg/mL and minimum bactericidal concentration (MBC) value of 100 mg/mL. The MIC index (MBC/MIC) was 2 for MRSA [ 13 ].

Antifungal activity

Ethanol extract of P. sarmentosum leaves (0.9 mg/disc) inhibited the growth of oral Candida albicans (inhibition zone = 10.81 ± 0.30 mm) using disk diffusion method. MBC value of the extract was 1.25 mg/mL for C. albicans and 2.5 mg/mL for Aggregatibacter actinomycetemcomitans using broth microdilution method [ 14 ].

Methanol extract of P. sarmentosum leaves (2.5% w/v) inhibited 100% of Colletotrichum gloesporioides mycelial growth while the chloroform extract (2.5% w/v) inhibited only 77.75% growth. Both extracts (2.5% w/v) also inhibited 100% of C. gloeosporioides spore germination [ 15 ].

Antiviral activity

Ethanol extract of P. sarmentosum leaves showed antiviral activity on vesicular stomatitis virus (VSV) (MIC value 0.02 mg/mL) using simplified plaque reduction assay [ 16 ].

Antituberculosis activity

Methanol extract and its ethyl acetate and chloroform fractions of P. sarmentosum leaves inhibited the growth of Mycobacterium tuberculosis with MIC value of 12.5 µg/mL (methanol extract), 3.12 µg/mL (for both ethyl acetate and chloroform fractions). The combination of isoniazid and ethyl acetate fraction of P. sarmentosum leaves (100 µg/mL) at a ratio of 1:3 in serial dilution gave fractional inhibitory concentration index (FICI) of 0.58 and MIC value of 0.5 µg/mL towards M. tuberculosis [ 18 ].

Both ethanol and aqueous extracts of P. sarmentosum leaves  inhibited the growth of  M. tuberculosis with MIC value of 12.5 µg/mL and MBC value of 12.5 µg/mL comparable to isoniazid (0.50 µg/mL) [ 19 ].

Anti-oxidant activity

Ethanol extract of P. sarmentosum leaves (0.1 mg/mL) also showed anti-oxidant activities with DPPH radical scavenging activity (21.82 ± 2.13%) compared to butylated hydroxyanisole (BHA) (34.93 ± 2.41%), quercetin (28.13 ± 1.95%) and vitamin E (10.98 ± 1.68%). The extract (0.1 mg/mL) also showed anti-oxidant activity (17.59 ± 3.2%) comparable to BHA (21.49 ± 2.41%) using β-carotene linoleate assay [ 19 ].

Methanol extract of P. sarmentosum leaves was also reported to have high β-carotene bleaching activity with anti-oxidant index of 13.0 ± 0.84 [ 17 ]. The extract (250 µg/mL) also showed xanthine/xanthine oxidase superoxide scavenging activity of 87.6% while naringenin isolated from the methanol extract showed 75.7% activity which is comparable to superoxide dismutase standard (100%) [ 20 ].

Rutin and vitexin (10-400 µm, each) isolated from the aqueous extract of P. sarmentosum leaves showed cytoprotective effect against oxidative stress caused by hydrogen peroxide (H2O2) in human umbilical vein endothelial (HUVEC) cells[ 21 ].

Methanol, aqueous and hexane extracts of P. sarmentosum leaves (150-300 µg/mL) significantly (p < 0.05) decreased malondialdehyde level, superoxide dismutase, catalase and glutathione peroxidase in HUVEC cells treated H2O2 compared to HUVEC cells treated with H2O2 only [ 22 ].

Methanol extract of P. sarmentosum leaves showed antioxidant activity with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 = 129.65 ± 1.04 µg/mL) compared to ascorbic acid (IC50  = 4.15 ± 0.50 µg/mL). Total phenolic content of the extract was found to be 50.01 mg GAE/g dry weight (DW) [ 23 ].

Methanol extract of P. sarmentosum leaves (125 mg/kg/day) was administered orally to male Wistar rats for 28 days before the induction of oxidative stress using carbon tetrachloride (CCl4). A significant (p < 0.05) decrease in lung thiobarbituric acid reactive substances (TBARS) level and lung glutathione peroxidase (GPx) activity was observed in treated rats compared to CCl4 induced control group [ 24 ].

Ethanol extract of P. sarmentosum leaves (250 and 500 mg/kg/day) was administered orally to male Sprague Dawley rats for 14 days before the induction of oxidative stress using carbon tetrachloride (CCl4). A significant decrease in TBARS level (p < 0.05) as well as increase in superoxide dismutase level (p < 0.05), catalase level (p < 0.05) and total plasma antioxidant activity (p < 0.05) were observed in treated rats compared to CCl4 induced control group [ 25 ].

Aqueous extract of P. sarmentosum leaves showed anti-oxidant activities with DPPH radical scavenging activity of 46.84% and β-carotene antioxidant protection factor of 1.11.Total phenolic content of the extract was found to be 10.98 mg GAE/g DW [ 26 ].

Aqueous extract showed antioxidant activities with DPPH radical scavenging activity (15.44%) compared to vitamin C (≈90%), ferric reducing antioxidant potential (FRAP) activity (377.41 mmol) compared to vitamin C (≈1700 mmol) and β-Carotene bleaching activity (17.6%) compared to vitamin C (≈11%) [ 27 ].

The boiled aqueous extract showed antioxidant activity with DPPH radical scavenging activity (38-40%) compared to butylated hydroxytoluene (BHT) (~85%). The FRAP activity (98.76 mmol) was lower compared to BHT (1000 mmol). Total phenolic content of the extract was found to be 10.92 mg/g DW [ 27 ]. 

Aqueous extract of P. sarmentosum leaves showed antioxidant activity with DPPH radical scavenging activity (IC50 = 27.12 mg/mL) compared to vitamin C [ 28 ].  

Anti-inflammatory activity

Methanol extract of P. sarmentosum leaves (50-100 µg/mL) significantly decreased nitric oxide (NO) production at 100 µg/mL (p < 0.001) and at 50 µg/mL (p < 0.05) in murine monocytic macrophages (RAW 264.7) cells treated with recombinant mouse interferon/ lipopolysaccharide (IFN-g/LPS) compared to IFN-g/LPS treated group only. The extract also showed moderate NO inhibitory activity (IC50 = 60.24 ± 2.39 µg/mL) compared to L-NG-nitroarginine methyl ester (L-NAME) (0.008 ± 0.1 µg/mL) in RAW 264.7 cells treated with IFN-g/LPS [ 23 ].

Methanol extract of P. sarmentosum leaves (50-200 mg/kg) was administered orally as a single dose to male Wistar rats before the induction of paw edema using carrageenan. After three hours, a significant inhibition of paw edema (p < 0.05 at 50 mg/kg, p < 0.01 at 100 mg/kg and p < 0.01 at 200 mg/kg) was observed in treated rats compared to distilled water treated group [ 29 ].

Methanol extract of P. sarmentosum leaves (300 mg/kg) was administered orally as a single dose to Wistar albino rats one hour before the induction of paw edema using carrageenan. A significant (p ≤ 0.01) inhibition of paw edema was observed in treated rats compared to control group [ 31 ].

Methanol extract of P. sarmentosum leaves (300 mg/kg) was administered orally as a single dose to Wistar albino rats before the induction of paw edema using dextran. After three hours, a significant (p ≤ 0.01) inhibition of paw edema was observed in treated rats compared to control group [ 31 ].

Aqueous extract of P. sarmentosum leaves (30-300 mg/kg) was administered subcutaneously as a single dose to Sprague Dawley rats 30 minutes before the induction of paw edema using carrageenan. A significant (p < 0.05) decrease in paw edema volume was observed in treated rats compared to dimethylsulfoxide treated group [ 30 ].

Antinociceptive activity

Methanol extract of P. sarmentosum leaves (200 mg/kg) was administered intraperitoneally as a single dose to male Balb/c mice for 30 minutes before the induction of abdominal constriction using acetic acid. A significant (p < 0.05) decrease in the number of abdominal constriction was observed in treated mice compared to 5% Tween-20 treated group
[ 23 ].  

Aqueous extract of P. sarmentosum leaves (30-300 mg/kg) was administered subcutaneously as a single dose to male Balb/c mice for 30 minutes before the induction of abdominal constriction using acetic acid. A significant (p < 0.05) dose dependent decrease in writhing response was observed in treated mice compared to saline treated group
[ 30 ].

Aqueous extract of P. sarmentosum leaves (30-300 mg/kg) was administered subcutaneously as a single dose to male Balb/c mice 30 minutes before the hot plate test. A significant (p < 0.05) dose dependent increase in the mean of latency time to discomfort reaction was observed in treated mice compared to saline treated group [ 30 ].

Anti-atherosclerosis activity

Standard diet enriched with 1% cholesterol and aqueous extract of P. sarmentosum leaves  (500 mg/kg/day) administered orally to male New Zealand white rabbits for a duration of 10 weeks significantly (p < 0.05) decreased inflammation markers (vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1) and C-reactive protein (CRP) compared to cholesterol diet group [ 28 ].  

Standard diet enriched with 1% cholesterol and aqueous extract of P. sarmentosum leaves (500 mg/kg/day) administered orally to male New Zealand white rabbits for a duration of 10 weeks significantly (p < 0.05) decreased atherosclerotic lesion area and reduced the thickening of tunica intima layer in rabbits aorta compared to cholesterol diet group [ 32 ].

Standard diet enriched with 1% cholesterol and methanol extract of P. sarmentosum leaves (62.5-250 mg/kg/day) administered orally to male New Zealand white rabbits for duration of 10 weeks significantly decreased the area of fatty streak (p ≤ 0.01)  and  reduced thickening of the intima and foam cell (p ≤ 0.01) in rabbit abdominal aorta compared to cholesterol diet group [ 33 ].

Concomitant treatment of aqueous extract of P. sarmentosum leaves (150 µg/mL) and H2O2 significantly decreased mRNA expression of cellular adhesion molecule (ICAM-1) (p < 0.01) and NADPH oxidase 4 (Nox4) (p < 0.05). The treatment also significantly increased the antioxidant enzymes; SOD1 (p < 0.05), catalase (p < 0.01) and GPx (p < 0.05) in HUVEC cells compared to control [ 34 ].

Aqueous extracts of P. sarmentosum leaves (150 µg/mL) significantly (p < 0.05) increased nitric oxide, endothelial nitric oxide synthase (eNOS) protein level, eNOS mRNA expression and eNOS enzyme activity in HUVEC cells compared to control [ 35 ].

Antidiabetic activity

Chaplupyrrolidones B isolated from the methanol extract of P. sarmentosum leaves inhibited α-glucosidase activity (IC50  430 ± 1.2 µm) compared to acarbose (404 ± 0.4 µm) [ 10 ].  

Aqueous extract of P. sarmentosum leaves showed approximately 70% inhibition of α-glucosidase activity [ 26 ].

Aqueous extract of P. sarmentosum leaves (0.125 g/kg/day) was administered orally for 28 days to streptozotocin-induced diabetic male Sprague Dawley rats. A significant decrease in fasting blood glucose (p < 0.05) and increase in body weight (p < 0.05) was observed in treated rats compared to diabetic group. Less ultrastructural degenerative changes in cardiac tissue and proximal aorta were also observed in treated rats compared to diabetic group [ 36 ].

Anti-osteoporosis activity

Aqueous extract of P. sarmentosum leaves (125 mg/kg/day) was administered orally for six weeks to ovariectomized female Sprague Dawley rats after closed fracture of the rats’ right femora. The median fracture healing score was significantly (p < 0.05) higher in treated rats compared to ovariectomized control rats. Histologically, the formation of woven bone and the remodeling of woven bone to lamellar bone were observed in treated rats [ 37 ].

A radiological study showed a significant decrease in total callus axial volume (p < 0.05) and callus score (p < 0.05) and increase in fracture healing score (p < 0.05) in treated rats compared to ovariectomized control rats. The soft calluses had been replaced by hard callus (woven bone), which was being remodelled into lamellar bone in treated rats [ 38 ].

Aqueous extract of P. sarmentosum leaves (125 mg/kg/day) was administered orally together with intramuscular dexamethasone for two months to adrenalectomized male Sprague Dawley rats (aged 43 months old). A significant increase in 11 β-HSD1 dehydrogenase activity (p < 0.05) that deactivated cortisol was observed. Subsequently this lead to the decreased expression of 11 β-HSD1 (p < 0.05) in bones of treated rats compared to dexamethasone-treated adrenalectomized rat [ 39 ].

Cytotoxicity activity

The ethanol extract of P. sarmentosum leaves showed cytotoxicity effect on human cervical carcinoma cells (HeLa) (cytotoxic dose at 50% (CD50) = 0.1 mg/mL) using microtitration cytotoxicity assay [ 16 ].

Methanol, aqueous and hexane extracts of P. sarmentosum leaves (0-1000 µg/mL) showed no cytotoxicity effect on HUVEC cells after 72 hours of incubation using MTT assay. The extracts also protected HUVEC cells against the cytotoxicity effect of H2O2 (Effective concentration at 50% (EC50) = 150 µg/mL) after 24 hours of incubation using MTT assay [ 22 ].  

Ethanol extract of P. sarmentosum leaves showed cytotoxicity effect (IC50 = 12.5 µg/mL) on human hepatocellular carcinoma (HepG2) compared to tamoxifen (IC50 = 3 µg/mL) after 72 hours of incubation using MTT assay. There was no cytotoxicity effect on Chang cell (normal liver cell) compared to tamoxifen (IC50 = 18.6 µg/mL). The extract (1.5-200 µg/mL) significantly (p < 0.05) decreased the viable HepG2 cells compared to untreated cells after 72 hours of incubation using trypan blue staining assay [ 40 ].

Anti-angiogenic activity

Pellitorine  (50 µg/mL) and sarmentine (50 µg/mL) isolated from chloroform extract of P. sarmentosum leaves showed low anti-angiogenic activity (30%) compared to suramin sodium (100%) in rat aorta ring model. The antiangiogenic activity of chloroform extract (45 µg/mL) was 50% [ 41 ].

SAFETY INFORMATION

Preclinical studies (Toxicology studies)

Acute toxicity

Methanol extract of P. sarmentosum leaves (5000 mg/kg) was administered orally as a single dose to male and female mice. The toxicity effect was observed for seven days and showed no toxic effect (LD50 > 5000 mg/kg) [ 29 ].

Ethanol extract of P. sarmentosum leaves (2000 mg/kg) was administered orally as a single dose to female Sprague Dawley rats (aged 8-12 weeks old). The toxicity effect was observed for 14 days and showed no toxic effect (LD50 > 2000 mg/kg) [ 35 ].

Oral single dose acute toxicity study using aqueous mixture of dried powder of P. sarmentosum leaves on female Sprague Dawley rats (aged between 8 and 12 weeks old) showed no toxic effect on the parameters observed which includes behaviors, body weight, food and water intakes. All rats were observed for 14 days prior to necropsy. No death was found throughout the study period. Necropsy revealed no significant abnormality. Approximate lethal dose (LD50) is more than 2,000 mg/kg body weight [ 42 ].

Clinical Studies

Information and data have not been established.

Others (Adverse reaction, contraindication, side effect, warning, precaution)

Information and data have not been established.

DOSAGE

Information and data have not been established.

STORAGE

Store below 30°C. Protect from light and moisture.

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