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Piper retrofractum

Piper retrofractum Vahl, commonly known as Javanese long pepper or Balinese long pepper, is a dioecious, evergreen climbing shrub in the family Piperaceae, native to Southeast Asia, including the Philippines, Indonesia, Malaysia, Thailand, Vietnam, Cambodia, Laos, and southern China.^[1] This liana grows up to 10 meters long, supported by adhesive roots, with glabrous, coriaceous leaves that are ovate to oblong, measuring 8–20 cm long and 3–13 cm wide, often featuring sunken gland dots.^[2] Its erect or patent spikes produce cylindrical infructescences 2–4 cm long, bearing connate berries that are green and pungent when unripe, turning red-brown upon maturity.^[2] The plant thrives in wet tropical biomes, particularly in deciduous forests on poor soils up to 600 m altitude, thickets at low elevations, and even along beaches, with semi-wild populations in areas like the Ryukyu Islands.^[1]^[2] It has been introduced and cultivated in regions including Bangladesh, northeastern India (e.g., East Himalaya), where it is propagated vegetatively by stem cuttings and often trained on supports like trees.^[1]^[3]^[2] Piper retrofractum is valued for its edible fruits, which are dried and used as a spice in curries, pickles, and preserves, offering a flavor more pungent and sweeter than black pepper (Piper nigrum).^[3]^[2] The berries contain piperine, resins, starch (44–49%), and essential oils (about 1% yield), contributing to their culinary and medicinal properties.^[2] In traditional medicine, particularly Ayurveda where it is known as chavya, the roots treat colic and dyspepsia, leaves alleviate postpartum fevers, and fruits address coughs, colds, diarrhea, digestive disorders, and conditions like hemorrhoids; leaf extracts also serve as a mouthwash.^[3]^[2] Additionally, the plant yields phenolic compounds with antioxidant activity, and its wood or roots produce dyes ranging from pale brown to brownish-red.^[3] Historically, Java exported 200–250 tons annually in the 1920s, highlighting its economic significance as a spice crop.^[2]

Taxonomy

Classification

Piper retrofractum is classified within the kingdom Plantae, phylum Tracheophyta, class Magnoliopsida, order Piperales, family Piperaceae, genus Piper, and species P. retrofractum.^[4] The species was first described by Martin Vahl in 1804, establishing its formal taxonomic authority.^[4] Within the genus Piper, which comprises approximately 2,000–2,500 species of primarily tropical vines and shrubs, P. retrofractum is distinguished from closely related taxa such as Piper longum (Indian long pepper) by its Southeast Asian origin, as opposed to the South Asian distribution of P. longum, along with differences in fruit morphology, such as the more curved spikes in P. retrofractum, and variations in microscopic stem and root structures observable via transverse sections.^[4]^[5] Morphological, anatomical, and genetic analyses further support these distinctions, confirming P. retrofractum as a separate lineage adapted to insular tropical environments.^[6] The Piperaceae family, to which P. retrofractum belongs, represents an early-diverging clade of angiosperms, with the genus Piper exhibiting a pantropical distribution and a climbing habit that has evolved multiple times within the family, facilitating diversification in humid forest understories.^[7] This evolutionary context underscores the family's role as a model for studying rapid speciation in basal angiosperms.^[8]

Synonyms

Piper retrofractum has several scientific synonyms reflecting its taxonomic history. Key heterotypic synonyms include Piper chaba W. Hunter (1809), Piper officinarum (Miq.) C.DC. (1869), and Chavica retrofracta Miq. (1844).^[2]^[3] These names arose from early descriptions and reclassifications within the Piperaceae family.^[9] The specific epithet retrofractum derives from Latin "retro" (backward) and "fractus" (bent or broken), alluding to the reflexed (backward-bending) peduncle of the fruiting spike, a distinctive morphological feature.^[10] This nomenclature was first established by Martin Vahl in 1804.^[1] Historically, the species was initially placed in the genus Chavica by Miquel in the mid-19th century before being transferred back to Piper, aligning with modern classifications that recognize over 2,000 species in the genus.^[2] This shift occurred during 19th-century botanical revisions, consolidating related taxa under Piper.^[3] Common names often incorporate regional spice traditions, such as Balinese long pepper and Javanese long pepper, while in Malay it is known as "cabai jawa" (Javanese chili).^[2]^[1] These vernacular terms highlight its cultural significance in Southeast Asian cuisines and medicine.

Description

Morphology

Piper retrofractum is a dioecious, evergreen climbing liana up to 10 m long in the family Piperaceae, requiring support from trees, trellises, or other structures for growth.^[3]^[11]^[2] The plant is perennial with soft woody stems that are terete, striated, and measure approximately 2-4 mm in diameter, often developing adhesive roots to aid in climbing.^[12]^[11] Its root system consists of a main root with numerous lateral roots, providing stability and support for propagation in cultivation.^[13]^[14] The leaves are alternate, simple, and glabrous, arranged spirally along the stems. They are short-petioled (5-11 mm long, sheathed at the base) with blades that are narrowly elliptic, ovate-oblong, or elliptic-lanceolate, measuring 8–20 cm long and 3–13 cm wide, with sunken gland dots on the abaxial surface.^[12]^[11]^[2] The leaf bases are rounded to slightly asymmetric or oblique, with an acuminate to acute apex, and the blades are coriaceous, densely glandular, and penninerved with 7-11 lateral veins on each side of the midvein.^[12]^[11]^[2] Piper retrofractum is dioecious, with leaf-opposed inflorescences forming spikes. Male spikes are slender, 3.8-8.5 cm long and 2.5-4.5 mm in diameter, with sessile, peltate, orbicular bracts (1-1.2 mm wide) and 2-3 stalkless stamens bearing broadly ellipsoid anthers.^[12]^[11] Female spikes are 3-6.5 cm long and 6.5-11 mm wide when mature, fleshy, cylindrical, and turn red, featuring ovaries immersed in the rachis and three short, recurved, ovate-acute stigmas.^[12]^[11] The fruits develop as spherical berries that are densely packed and partially connate to the rachis in dense, rod-like spikes 2–4 cm long, with rounded apices and subglobose to obovoid-globose seeds approximately 2-2.5 mm long.^[12]^[11]^[2]

Reproduction

Piper retrofractum is a dioecious species, featuring separate male and female plants, with unisexual flowers densely arranged on pedunculated spikes that emerge from the leaf axils. Male spikes are typically longer, bearing flowers with 2-3 stamens, while female spikes are shorter and feature flowers with a peltate stigma. In tropical climates, flowering occurs year-round, with spikes developing on plagiotropic branches.^[2]^[15]^[16] Pollination in P. retrofractum is primarily entomophilous, facilitated by insects such as bees and flies that visit the inflorescences; the species exhibits self-incompatibility inherent to its dioecious nature, preventing self-fertilization. Flower emergence to fertilization, marked by dried-up flowers, spans 15-30 days.^[17]^[15] Following pollination, fruit development proceeds with berries forming along the spike, maturing from green to orange or dark red in approximately 1.5–2 months; each berry is a small drupe containing a single seed. Seed dispersal occurs primarily through endozoochory, with birds and mammals consuming the aromatic fruits and excreting the viable seeds.^[15]^[2] The dioecious reproductive system of P. retrofractum necessitates the presence of both male and female plants in proximity for successful seed production in natural populations and cultivation settings, as male plants provide pollen essential for female fruit set.^[18]

Distribution and habitat

Native range

Piper retrofractum is native to the Philippines, with wild populations reported across the Malesian floristic region including Java in Indonesia, southern Thailand, Indo-China (including Vietnam, Laos, and Cambodia), Peninsular Malaysia, and surrounding areas.^[2]^[3]^[1] Historical records from herbarium specimens dating to the 18th and 19th centuries confirm these wild distributions, with collections primarily from the Malesian region, including early descriptions from Java and surrounding areas that document its occurrence in undisturbed tropical thickets and forests. These records, preserved in institutions such as the Royal Botanic Gardens Kew, underscore the species' long-established presence in this biogeographic zone without evidence of broader natural extension beyond Malesia.^[1]^[12] The species is not considered endangered globally, though local populations face threats from habitat loss due to deforestation and agricultural expansion in its native ranges. As of 2023, a new record of the species has been documented in West Bengal, India.^[19]

Ecological preferences

Piper retrofractum thrives in tropical lowland rainforests, secondary forests, and forest edges across Southeast Asia, where it commonly occurs in coastal regions and inland areas up to 1000 m in altitude.^[15]^[20] The plant prefers partial shade within these habitats, often climbing on supporting trees or structures to access filtered sunlight, and favors moist, well-drained soils such as sandy loam or those rich in organic matter with a pH range of 4-8.^[15] This species is adapted to humid tropical climates characterized by annual rainfall of 1250-2500 mm, with 5.7-6.8 wet months and humidity levels of 40-90%, though it demonstrates resilience in areas with up to 6-7 dry months and as low as 960 mm annual rainfall.^[15] It grows effectively at temperatures typical of tropical environments, generally between 20-30°C, and shows tolerance to a variety of soil types including laterite, podzolic, and rocky substrates.^[15]^[21] Ecologically, P. retrofractum serves as a host for arthropod pests such as the spider mite Tetranychus okinawanus and various mealybugs, which can infest its vines in natural and semi-natural settings.^[20] Its fruits attract frugivorous birds, including bulbuls, which consume and aid in seed dispersal within forest understories. The plant's climbing habit, supported by adhesive roots, enables it to reach canopy light gaps, while its overall adaptability to suboptimal moisture and soil conditions contributes to its persistence in disturbed forest margins.^[15]

Cultivation

Propagation methods

Piper retrofractum is primarily propagated vegetatively through stem cuttings sourced from healthy, year-old mother plants to maintain desirable traits and ensure uniformity. Cuttings are typically taken from climbing, ground, or fruit branches, with those from climbing branches preferred for their higher vigor and success rates. Standard cuttings measure approximately 10 cm in length, consisting of two segments or three internodes, and are selected from semi-woody stems to leverage the plant's climbing vine morphology for optimal rooting. These are dipped in auxin-based rooting hormones such as IBA or Rhizopon AA to promote adventitious root development, achieving rooting in shaded, moist conditions within 1-3 months.^[15]^[22]^[23]^[23] Rooting media commonly include a mixture of soil, sand, and cow dung or manure in a 1:1:1 or 3:1 ratio, providing aeration and nutrients while preventing waterlogging. Success rates vary by cutting type, with climbing branch cuttings rooting at 75%, ground branch at 66%, and fruit branch at 38%, often enhanced by natural plant growth regulators like cow urine soaks for improved root length and shoot emergence. Propagation is best timed at the onset of the rainy season, when higher humidity supports outdoor rooting without excessive wilting.^[22]^[23]^[22]^[23] Seed propagation, though feasible, is less favored due to the plant's cross-pollination leading to high genetic variability, slower initial growth, and lower viability compared to vegetative methods. Seeds are extracted from ripe fruits and sown directly in prepared beds or polybags under shaded, humid conditions, but specific germination protocols remain underdocumented, with general estimates suggesting 2-6 weeks under tropical warmth.^[23]^[24] For mature plants or to produce disease-free stock, air-layering serves as an effective vegetative alternative for Piper species, involving girdling branches and wrapping with moist sphagnum moss or soil to induce roots before detachment. Tissue culture offers a micropropagation option, utilizing leaf explants on Murashige and Skoog medium supplemented with 2,4-D (1.0 mg/L) and BAP (1.0-2.0 mg/L), yielding friable callus in 15 days for subsequent shoot and root regeneration.^[25]

Growing requirements

Piper retrofractum thrives in fertile, loamy soils that are well-drained and rich in organic matter, with a pH range of 4 to 8, to prevent waterlogging and support root development.^[15] Nutrient-rich alluvial or volcanic soils are particularly suitable, enhancing nutrient uptake in tropical agroforestry systems.^[26] The plant requires a tropical or subtropical climate with high humidity (80-90%) and annual rainfall of 1250 to 2500 mm, though it can tolerate up to 4000 mm in humid conditions; temperatures around 25°C and altitudes from 0 to 1000 m are ideal.^[15]^[26] It prefers partial shade (50-75% light intensity) but adapts to full sun with adequate moisture, and plants should be spaced 1.5 to 2.0 m apart on living supports like trees, with 1 to 3 vines per support for climbing growth.^[15] Maintenance involves regular pruning to maintain vine height at about 2 m, remove unproductive or hanging branches, and promote bushiness, alongside weeding to manage competition.^[15] Fertilization typically includes organic manure such as 15 kg of cow dung per tree annually, supplemented by NPK fertilizers at rates like 60 g per young tree, to sustain growth and productivity.^[15] Common pests include aphids and nematodes (Radopholus similis), while fungal diseases like foot rot (Phytophthora sp.) require microclimate management, pruning, and targeted controls to minimize damage.^[15]^[27] Harvest occurs 2 to 3 years after planting, with fruits picked at the orange to red stage 3 to 5 times per year at 15- to 25-day intervals, then dried for 3 to 5 days; yields reach 1 to 1.5 kg of dried fruit per plant annually at peak production.^[15]^[26]

Uses

Culinary applications

The fruits of Piper retrofractum, commonly known as Javanese long pepper, exhibit a hot, earthy, and sweet flavor profile that is more pungent than black pepper (Piper nigrum), with an agreeable aromatic taste attributed to compounds like piperine.^[2]^[28] This spice is versatile in form, employed whole for subtle infusion, ground into powder for even distribution in blends, or extracted as an essential oil with a ginger-like aroma for flavoring dishes.^[2] In Indonesian cuisine, P. retrofractum plays a key role in traditional preparations, such as sambals—chili pastes that predate the introduction of New World chilies—and curries like rendang, where ground fruits contribute warmth and complexity to slow-cooked meats and sauces.^[29]^[30] Thai cooks incorporate it into salads, soups, and stir-fries, leveraging its nuanced heat to balance sour and savory elements.^[31] In Indian cuisine, it substitutes for Indian long pepper (Piper longum) in masalas and vegetable pickles (achar), enhancing spice mixes with its robust pungency.^[28] Preparation methods emphasize moderation due to the spice's intensity; dried fruit spikes are typically toasted, ground into fine powder, or steeped in oils for infusion, with small quantities—often less than 1 g per serving—sufficing to impart flavor without overwhelming other ingredients.^[28] Nutritionally, 100 g of the dried fruits yields approximately 324 kcal, substantial dietary fiber (28.8 g), and minerals including iron, while being rich in antioxidants that support its role in everyday diets.^[32]^[33]

Medicinal properties

In traditional Ayurvedic medicine, known as Chavya, Piper retrofractum is used to address digestive disorders such as indigestion, constipation, and abdominal pain, as well as respiratory issues including cough, asthma, and bronchitis; the fruit also serves as an aphrodisiac to enhance vitality.^[34] In Indonesian Jamu practices, the plant functions as a tonic for digestive ailments like flatulence and loss of appetite, respiratory conditions such as colds and mild asthma, and as an aphrodisiac to improve sleep and sexual function.^[35]^[36] Root decoctions are specifically employed to alleviate stomach ailments, including bloating and worm infestations.^[34] Contemporary studies validate several of these traditional applications through identified pharmacological mechanisms. The ethanol extract demonstrates anti-inflammatory effects by downregulating cyclooxygenase-2 (COX-2) expression and suppressing proinflammatory cytokines like IL-6 and IL-1β via inhibition of the TLR4/NF-κB pathway, with piperine contributing significantly to this activity.^[37] It also exhibits moderate antioxidant capacity, with ethyl acetate and n-hexane extracts showing IC<sub>50</sub> values of 57.66–66.12 μg/mL in DPPH assays.^[38] Furthermore, methanol extracts possess antimicrobial properties, effectively inhibiting Escherichia coli with a minimum inhibitory concentration of 22.5 μg/μL and inhibition zones up to 2.0 mm.^[39] Evidence from animal models supports its efficacy in gastrointestinal disorders; for instance, a green tea extract containing Piper retrofractum fruit (100–200 mg/kg) ameliorated dextran sulfate sodium-induced colitis in mice by reducing colon shortening, histological damage, and inflammatory markers such as TNF-α, IL-6, COX-2, and NF-κB activity.^[40] No significant toxicity to liver or kidney function was observed at doses up to 5 g/kg body weight in preclinical evaluations.^[38] Typical dosages include 1–2 g per day of powdered fruit or root for oral use, while extracts are applied topically for anti-arthritic relief.^[34] Due to its heating potency, which may exacerbate gastritis or burning sensations, it is contraindicated during pregnancy and for individuals with Pitta imbalances; consultation with a healthcare provider is advised for lactating women or long-term use.^[34]

Phytochemistry

Active compounds

The fruits of Piper retrofractum primarily contain alkaloids as key active compounds, with piperine being the predominant one at concentrations of 3.1–4.5% of the dry weight.^[41] Piperine is typically isolated from fruit extracts using solvent methods such as methanol or ethanol extraction followed by chromatography.^[42] Essential oils from the fruits and roots are obtained upon steam distillation, with composition analyzed primarily through gas chromatography-mass spectrometry (GC-MS).^[36] Major constituents include β-caryophyllene (up to 27.71% in mature fruits), limonene (around 0.79%), and sabinene, alongside monoterpenes like α-pinene and myrcene.^[36] These volatile compounds vary by plant part, with fruits showing higher sesquiterpene content compared to roots. Additional metabolites encompass flavonoids, lignans, and steroids, extracted via solvent partitioning with solvents like ethyl acetate or methanol.^[43] Lignans (e.g., (-)-sesamin) and steroids are present in lower abundances across aerial parts. Amides such as retrofractamide A have been identified in fruit extracts. Piperine content is highest at the green-mature stage and decreases in more advanced maturity stages.^[33] Regional variations affect essential oil profiles, with samples from low-altitude areas like Lampung, Indonesia, exhibiting distinct piperine levels in ethanol extracts relative to higher-altitude regions.^[44]

Pharmacological effects

Piperine, a key alkaloid in Piper retrofractum, enhances the bioavailability of co-administered drugs such as curcumin by inhibiting efflux transporters like P-glycoprotein and metabolic enzymes including CYP3A4, thereby reducing first-pass metabolism and increasing intestinal absorption.^[45]^[46] This mechanism has been demonstrated in both in vitro and in vivo models, where piperine at concentrations of 20-100 μM significantly boosts plasma levels of substrates like resveratrol and silybin by 2- to 15-fold.^[47]^[48] In cancer research, piperine exhibits anti-tumor effects through induction of apoptosis in various cell lines; for instance, it upregulates pro-apoptotic proteins like Bax and caspase-3 while downregulating anti-apoptotic Bcl-2 in ovarian and melanoma cells, leading to cell cycle arrest at G2/M phase.^[49]^[50] These effects occur via reactive oxygen species generation and mitochondrial pathway activation, with IC50 values ranging from 20-50 μM in vitro.^[51]^[52] In vivo studies in rodent models further support these pharmacological activities. Piperine provides gastroprotective effects against ethanol- or indomethacin-induced gastric ulcers in rats, reducing the ulcer index by 36-48% at oral doses of 50-100 mg/kg through enhancement of mucosal prostaglandin levels and antioxidant enzyme activities like superoxide dismutase.^[53] Analgesic effects have been observed in mouse models of acetic acid-induced writhing and hot-plate tests, where piperine at 10-20 mg/kg produces dose-dependent pain inhibition mediated by opioid and GABAergic pathways, achieving up to 60% reduction in writhing responses, though less potent than aspirin in direct comparisons.^[54]^[55] Extracts of P. retrofractum also show anti-inflammatory activity in imiquimod-induced skin inflammation in mice, suppressing NF-κB signaling and proinflammatory cytokines like TNF-α by 40-70% at doses of 50-200 mg/kg.^[56] The toxicity profile of P. retrofractum constituents indicates low acute risk; piperine has an oral LD50 greater than 514 mg/kg in adult rats, with no observed mortality or significant organ damage at doses up to 100 mg/kg in subacute studies.^[57] However, potential interactions exist with CYP3A4-metabolized drugs, as piperine inhibits this enzyme, possibly elevating plasma levels of substrates like carbamazepine by 50-100%.^[58]^[59] Ethanolic extracts of the plant are generally safe, with no genotoxicity reported in Ames tests.^[60] Despite promising preclinical data, research gaps persist, including a scarcity of human clinical trials to validate efficacy and safety. As of 2025, recent studies have demonstrated anti-inflammatory effects of P. retrofractum extracts in skin inflammation models and cytotoxic activity against cervical cancer cell lines, suggesting further potential in oncology and dermatology, though additional validation is needed.^[37]^[61]

History

Traditional significance

Piper retrofractum, known locally as cabe jawa in Indonesia, has been documented in ancient Javanese inscriptions from the early tenth century as a valued spice alongside black and white pepper, highlighting its early integration into regional agriculture and trade. In traditional Indonesian contexts, it served dual roles as both a culinary spice and a medicinal herb, often incorporated into herbal preparations for digestive and respiratory ailments, reflecting its longstanding significance in pre-colonial societies.^[2] In Thai ethnobotanical traditions, Piper retrofractum, referred to as dipli or dipli-chueak, holds cultural importance as a "hot"-flavored plant used to enhance vitality through improved digestion, blood circulation, and as a component of trikatu formulations that balance bodily elements and promote overall well-being.^[62] These uses underscore its role in folk medicine for treating conditions like asthma, influenza, and hypertension, positioning it as a symbol of restorative energy in rural communities across Thailand's floristic regions.^[16] Among Malay communities in the pre-16th century Malay Archipelago, the fruit was a key trade item known as cabai, prized for its pungent flavor in local cuisines and medicines before the introduction of New World chilies (Capsicum spp.) shifted the term's application to the latter. This naming evolution illustrates its economic prominence in regional spice exchanges, where it was cultivated and traded as a native alternative to imported peppers.

Modern developments

Recent studies since 2000 have advanced the understanding of Piper retrofractum's bioactives, particularly its anti-inflammatory potential. A comprehensive 2019 review highlighted the anti-inflammatory activities of Piper species through modulation of pathways such as NF-κB.^[63] Subsequent research, such as a 2023 study, demonstrated that P. retrofractum extract ameliorates imiquimod-induced skin inflammation in mice by suppressing TLR4 signaling and NF-κB activity, reducing cytokine production.^[56] Genetic research has also progressed, with a 2023 comparative transcriptome analysis identifying genes associated with alkaloid diversity in P. retrofractum fruits, providing insights for breeding programs aimed at enhancing bioactive content.^[64] Commercialization of P. retrofractum has expanded, with cultivation primarily in Indonesia, India, and parts of Southeast Asia like Thailand and Malaysia for export of dried fruits and extracts. In Indonesia, it is harvested from wild and semi-cultivated sources in Java and exported to markets in Malaysia and beyond, supporting local economies through agroforestry systems.^[2] In India, dried fruits are traded at approximately ₹900 per kg (around $10.70 USD), reflecting demand for use in traditional formulations and modern products.^[65] The plant features in nutraceutical supplements for its piperine content, marketed for anti-inflammatory and bioavailability-enhancing effects in products like capsules and powders.^[66] Conservation efforts in Indonesia focus on protecting wild stocks of P. retrofractum through agroforestry initiatives that integrate it into sustainable farming systems. Programs in rural Java emphasize forest garden management to prevent overharvesting, recognizing the species as a high-value medicinal resource.^[67] Future prospects for P. retrofractum center on its piperine-derived applications in pharmaceuticals, particularly as a bioenhancer in drug delivery systems. Piperine improves the solubility and absorption of poorly bioavailable drugs by inhibiting efflux transporters like P-glycoprotein, with nanoformulations such as lipid carriers showing promise for targeted therapies.^[68] Ongoing research explores piperine-loaded mesoporous silica nanoparticles for controlled release, potentially advancing treatments for inflammation and cancer.^[69]

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https://pmc.ncbi.nlm.nih.gov/articles/PMC5876197/
[34]
Effects of Cabya (Piper retrofractum Vahl.) Fruit Developmental ... - NIH
Aug 21, 2022 · This study investigated the flavor variation characteristics and the diversity of VOCs in cabya fruits at different developmental stages.Missing: reproduction pollination dioecy
[35]
Piper retrofractum ameliorates imiquimod-induced skin inflammation ...
Sep 14, 2023 · Our findings suggest that Piper retrofractum extract possesses anti-inflammatory properties by reducing proinflammatory cytokine production through inhibition ...
[36]
A REVIEW OF PHYTOCHEMICAL AND PHARMACOLOGICAL ...
Aug 6, 2025 · Javanese chili (Piper retrofractum Vahl) is a traditional medicinal plant originating from Indonesia and has many pharmacological activities, ...
[37]
In Vitro Antimicrobial Activity of Piper retrofractum Fruit Extracts ...
Feb 14, 2020 · In addition, it was reported to possess gastroprotective and cholesterol-lowering properties which could be useful for application in ...
[38]
Green Tea Extract Containing Piper retrofractum Fruit Ameliorates ...
Recently, piperine has been shown to inhibit the levels of colonic NF-κB protein and the mRNA expression of pro-inflammatory mediators (TNF-α, IL-1β, IL-6, iNOS ...
[39]
Safety Aspects of the Use of Isolated Piperine Ingested as a Bolus
For adults (≥18 years), a daily dose of 250–420 mg for the unextracted powder of Piper nigrum fruits and a daily maximum dose of 14 mg for the use of piperine ...
[40]
[PDF] Isolation of Piperin From the Fruit of Piper Retrofractum - CORE
The optimum This paper will described the isolation of major compound from MeOH extract from the fruit of Piper retrofractum. Using several chromatography ...Missing: retrofractin | Show results with:retrofractin
[41]
[PDF] Phytopharmacological Investigations of Piper retrofractum Vahl.
In terms of morphological characteristics, all species in this genus possess three plant forms including creeping, climbing, and branching stems. In addition, ...Missing: botanical | Show results with:botanical<|separator|>
[42]
Piperine Levels in Java Chili and Black Fruits Extracts from Regions ...
Mar 31, 2021 · The results showed that the levels of piperine contained in the 95% ethanol extract of java chili fruit from low altitude (Lampung), medium ...
[43]
Piperine, a major constituent of black pepper, inhibits human P ...
In summary, we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4.
[44]
Black pepper and its pungent principle-piperine: a review of diverse ...
Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property.
[45]
Enhancing the bioavailability of resveratrol by combining it with ...
Conclusion: Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed ...
[46]
Piperine enhances the bioavailability of silybin via inhibition of efflux ...
The underlying mechanisms involved that piperine enhanced the absorption of silybin by inhibiting the efflux transporters including MRP2 and ...
[47]
Piperine alkaloid induces anticancer and apoptotic effects ... - PubMed
These results suggest that Piperine exerts potent anticancer effects on ovarian cancer cells and may prove beneficial in the management of ovarian cancer.
[48]
Antitumor and Apoptosis-inducing Effects of Piperine on Human ...
Piperine suppressed the growth of human melanoma cells by the induction of apoptosis via the inhibition of tumor growth of human melanoma cells and tumor ...
[49]
Mechanism of piperine in affecting apoptosis and proliferation of ...
The present study showed that PIP can induce the generation of ROS, thereby promoting the activation of mitochondrial apoptotic pathway and exerting anti- ...
[50]
Piperine Inhibits Cell Proliferation and Induces Apoptosis of Human ...
Dec 31, 2020 · BACKGROUND Piperine has been reported to inhibit proliferation and induce apoptosis in various cancer cells. This study aimed to explore the ...
[51]
Protective Action of Piperine Against Experimental Gastric Ulcer
Results: Pip 25, 50, 100 mg/kg ig protected animals from gastric ulceration in a dose-dependent manner. The inhibitory rates were 16.9%, 36.0%, and 48.3% in ...Missing: gastroprotective reduction
[52]
The analgesic and anticonvulsant effects of piperine in mice - PubMed
These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively.Missing: activity | Show results with:activity
[53]
Analgesic and anti-inflammatory activities of Piper nigrum L - PubMed
However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic ...
[54]
Piper retrofractum ameliorates imiquimod-induced skin inflammation ...
Sep 14, 2023 · Piper retrofractum extract possesses anti-inflammatory properties by reducing proinflammatory cytokine production through inhibition of NF-κB signaling pathway.Missing: pharmacological | Show results with:pharmacological
[55]
Acute and subacute toxicity of piperine in mice, rats and hamsters
The i.p. LD50 value was increased to 60 mg/kg body wt in adult female and 132 mg/kg body wt in weanling male mice. In adult female rats, the i.p. LD50 value was ...
[56]
Effect of Piperine on the Metabolism and Pharmacokinetics of ...
Accordingly, caution should be taken when PIP is used in combination with therapeutic drugs metabolized by CYP3A4 in addition to CBZ.
[57]
Predicting Food-Drug Interactions between Piperine and CYP3A4 ...
Oct 11, 2024 · These findings suggest that caution should be exercised when consuming amounts of black pepper equivalent to a daily intake of 20 mg piperine ...
[58]
Antioxidant and hepatoprotective activity of Piper retrofractum ...
The ethanol extracts of Piper retrofractum were investigated for antioxidant and hepatoprotective activity. Hepatoprotective activity against paracetamol- ...
[59]
Anti-Diabetic Effects and Molecular Mechanisms of Amide Alkaloids ...
Results indicated that retrofractamides A (1) and C (2) exerted anti-diabetic effect via activating PI3K/AKT pathway, and they promoted glucose consumption, ...Missing: retrofractum | Show results with:retrofractum<|control11|><|separator|>
[60]
(PDF) Ethnobotany of the Genus Piper (Piperaceae) in Thailand
Aug 9, 2025 · Additionally, the leaves are used for traditional remedies and folk customs, such as for weddings and housewarming ceremonies. More recently, ...
[61]
Piper retrofractum - Wikipedia
Piper retrofractum, the Balinese long pepper or Javanese long pepper, is a flowering vine in the family Piperaceae, cultivated for its fruit, which is usually ...Missing: authority | Show results with:authority
[62]
The Sea (Chapter 4) - Monsoon Islam
Apr 28, 2018 · ... trade in the Indian Ocean in the second half of the sixteenth century. ... and Javanese long pepper (Piper retrofactum, Vahl). For a fuller ...
[63]
Piper Species: A Comprehensive Review on Their Phytochemistry ...
Piper retrofractum Vahl. Piper retrofractum is said to have stimulant and carminative effects, and help to improve digestion. It is also used to treat ...
[64]
Comparative Transcriptome Analysis Reveals Genes Associated ...
Piper retrofractum, or Javanese long pepper, is a tropical plant from the Piperaceae family native to Southeast Asia. Many species of this family, such as Piper ...Missing: habitat | Show results with:habitat
[65]
Badi Pipli - Piper retrofractum - Javanese Long Pepper - Pippali, 1 Kg
Badi Pipli - Piper retrofractum - Javanese Long Pepper - Pippali, 1 Kg ; PIPLI (Long Pepper). ₹ 900/Kg ; Choti Peepli. ₹ 680/Kg ; Pippali Extract Piper Longum. ₹ ...
[66]
YUVIKA Pipal Choti | Pipali - Piper Retrofractum (100 Grams)
Ingredients: Pipal Choti | Pipali - Piper Retrofractum; Cuisine : Indian; Specialty: No Artificial Colors, Fresh & Pure; Country of Origin: India. See more ...Missing: market export
[67]
[PDF] Medicinal Plant Production System Management in Rural Java ...
Jan 3, 2025 · Indonesia recognizes medicinal plants as high-value resources for conservation ... Piper cubeba's collection; (b) Piper retrofractum in forest ...
[68]
Reforesting the island of Flores to ensure a common future
The Wild Pepper Tree (Piper retrofractum) is also used for postpartum preparations. ... Since 2015, Cœur de Forêt has been advocating for environmental and social ...
[69]
A Review on the Ecology, Evolution and Conservation of Piper ...
Aug 9, 2025 · Piper species in India have a high potential for future utilization; however, their conservation status and needs have not been widely reviewed.
[70]
Piperine loaded drug delivery systems for improved biomedical ...
In this review, we have exhaustively reviewed advanced and novel drug delivery systems to improve its biopharmaceutical attributes.
[71]
Development of Novel Piperine‐Loaded Mesoporous Silica ...
Jan 31, 2025 · They are used as a vehicle for drug delivery systems and other biological applications due to their excellent drug-loading efficiency ...