Parabroom

SCIENTIFIC RESEARCH ON THE FOLLOWING INGREDIENTS:

Wormwood

Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Wormwood

Abstract

Plants have been used since ancient times to cure certain infectious diseases, and some of them are now standard treatments for several diseases. Due to the side effects and resistance of pathogenic microorganisms to antibiotics and most drugs on the market, a great deal of attention has been paid to extracts and biologically active compounds isolated from plant species used in herbal medicine. Artemisia absinthium is an important perennial shrubby plant that has been widely used for the treatment of several ailments. Traditionally, A. absinthium has always been of pharmaceutical and botanical importance and used to manage several disorders including hepatocyte enlargement, hepatitis, gastritis, jaundice, wound healing, splenomegaly, dyspepsia, indigestion, flatulence, gastric pain, anemia, and anorexia. It has also been documented to possess antioxidant, antifungal, antimicrobial, anthelmintic, anti-ulcer, anticarcinogenic, hepatoprotective, neuroprotective, antidepressant, analgesic, immunomodulatory, and cytotoxic activity. Long-term use of A. absinthium essential oil may cause toxic and mental disorders in humans with clinical manifestations including convulsions, sleeplessness, and hallucinations. Combination chemotherapies of artemisia extract or its isolated active constituents with the currently available antibabesial or anti-malarial drugs are now documented to relieve malaria and piroplasmosis infections. The current review examines the phytoconstituents, toxic and biological activities of A. absinthium.

Source: Batiha GE, Olatunde A, El-Mleeh A, Hetta HF, Al-Rejaie S, Alghamdi S, Zahoor M, Magdy Beshbishy A, Murata T, Zaragoza-Bastida A, Rivero-Perez N. Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Wormwood (Artemisia absinthium). Antibiotics (Basel). 2020 Jun 23;9(6):353. doi: 10.3390/antibiotics9060353. PMID: 32585887; PMCID: PMC7345338.

Artemisia absinthium L.—Importance in the History of Medicine, the Latest Advances in Phytochemistry and Therapeutical, Cosmetological and Culinary Uses

Abstract

Artemisia absinthium—wormwood (Asteraceae)—is a very important species in the history of medicine, formerly described in medieval Europe as “the most important master against all exhaustions”. It is a species known as a medicinal plant in Europe and also in West Asia and North America. The raw material obtained from this species is Absinthii herba and Artemisia absinthium aetheroleum. The main substances responsible for the biological activity of the herb are: the essential oil, bitter sesquiterpenoid lactones, flavonoids, other bitterness-imparting compounds, azulenes, phenolic acids, tannins and lignans. In the official European medicine, the species is used in both allopathy and homeopathy. In the traditional Asian and European medicine, it has been used as an effective agent in gastrointestinal ailments and also in the treatment of helminthiasis, anemia, insomnia, bladder diseases, difficult-to-heal wounds, and fever. Today, numerous other directions of biological activity of the components of this species have been demonstrated and confirmed by scientific research, such as antiprotozoal, antibacterial, antifungal, anti-ulcer, hepatoprotective, anti-inflammatory, immunomodulatory, cytotoxic, analgesic, neuroprotective, anti-depressant, procognitive, neurotrophic, and cell membrane stabilizing and antioxidant activities. A. absinthium is also making a successful career as a cosmetic plant. In addition, the importance of this species as a spice plant and valuable additive in the alcohol industry (famous absinthe and vermouth-type wines) has not decreased. The species has also become an object of biotechnological research.

Source: Szopa A, Pajor J, Klin P, Rzepiela A, Elansary HO, Al-Mana FA, Mattar MA, Ekiert H. Artemisia absinthium L.-Importance in the History of Medicine, the Latest Advances in Phytochemistry and Therapeutical, Cosmetological and Culinary Uses. Plants (Basel). 2020 Aug 19;9(9):1063. doi: 10.3390/plants9091063. PMID: 32825178; PMCID: PMC7570121.

Effects of plumbagin on development of the parasitic nematodes Haemonchus contortus and Ascaris suum

Abstract

1. Plumbagin (5-hydroxy,2-methyl-1,4-naphthoquinone) inhibited the motility and survival of Haemonchus contortus first-stage larvae (L1) with an ED50 of 1 microgram/ml, but was less effective in preventing the development of H. contortus to infective third-stage larvae in a fecal slurry assay. 2. Of the structural analogs tested, plumbagin was the most potent in preventing development of L1 followed in decreasing order of potency by 1,4-naphthoquinone, 5-hydroxy-1,4-naphthoquinone (juglone) and 1,2-naphthoquinone. 3. Plumbagin had a biphasic effect on development of the fourth-stage Ascaris suum larvae that caused an increase in growth at low concentrations but was lethal at higher doses. 4. Plumbagin and 1,2-naphthoquinone partially inhibited embryonation of A. suum eggs.

Source: Fetterer RH, Fleming MW. Effects of plumbagin on development of the parasitic nematodes Haemonchus contortus and Ascaris suum. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1991;100(3):539-42. doi: 10.1016/0742-8413(91)90036-s. PMID: 1687553.

Garlic

Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae

Abstract

Background: Garlics and onions have been used for the treatment of diseases caused by parasites and microbes since ancient times. Trypanosomiasis and leishmaniasis are a concern in many areas of the world, especially in poor countries.

Methods: Trypanosoma brucei and Leishmania tarentolae were used to investigate the anti-parasitic effects of dichloromethane extracts of Allium sativum (garlic) and Allium cepa (onion) bulbs. As a confirmation of known antimicrobial activities, they were studied against a selection of G-negative, G-positive bacteria and two fungi. Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (LC-ESI-MS/MS).

Results: Chemical analyses confirmed the abundance of several sulfur secondary metabolites in garlic and one (zwiebelane) in the onion extract. Both extracts killed both types of parasites efficiently and inhibited the Trypanosoma brucei trypanothione reductase irreversibly. In addition, garlic extract decreased the mitochondrial membrane potential in trypanosomes. Garlic killed the fungi C. albicans and C. parapsilosis more effectively than the positive control. The combinations of garlic and onion with common trypanocidal and leishmanicidal drugs resulted in a synergistic or additive effect in 50% of cases.

Conclusion: The mechanism for biological activity of garlic and onion appears to be related to the amount and the profile of sulfur-containing compounds. It is most likely that vital substances inside the parasitic cell, like trypanothione reductase, are inhibited through disulfide bond formation between SH groups of vital redox compounds and sulfur-containing secondary metabolites.

Source: Krstin S, Sobeh M, Braun MS, Wink M. Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae. Medicines (Basel). 2018 Apr 21;5(2):37. doi: 10.3390/medicines5020037. PMID: 29690511; PMCID: PMC6023319.

Papain

In vitro efficacy of latex and purified papain from Carica papaya against Strongyloides venezuelensis eggs and larvae

Abstract

Latex from Carica papaya is rich in bioactive compounds, especially papain, which may help to control parasitic diseases. This study evaluated the efficacy of latex from C. papaya and purified papain against Strongyloides venezuelensis. The Egg Hatching Test (EHT) and the Larval Motility Test (LMT) using fresh and frozen latex (250mg/mL), lyophilized latex (34mg/mL), and purified papain (2.8 mg/mL) were performed. Albendazole (0.025 mg/mL) and ivermectin (316 ppm) were used as positive controls. EHT and LMT were carried out through the incubation of each solution with S. venezuelensis eggs or larvae (± 100 specimens), and results were analyzed after 48h (EHT) or 24, 48, and 72h (LMT). EHT showed that latex preparations at higher concentrations (1:10 to 1:100) resulted in partial or complete destruction of eggs and larvae inside the eggs. The result from the 1:1,000 dilution was similar to the positive control. LMT showed effectiveness in all the tested dilutions compared to negative controls. Purified papain showed a dose-dependent response in the EHT. Purified papain (2.8 mg/ mL) showed similar results to lyophilized latex at 1:1,000 in the EHT. Latex and purified papain from C. papaya were effective against S. venezuelensis eggs and larvae in vitro, suggesting their potential use as an alternative treatment for strongyloidiasis.

Source: Moraes D, Levenhagen MA, Costa-Cruz JM, Costa AP Netto, Rodrigues RM. In vitro efficacy of latex and purified papain from Carica papaya against Strongyloides venezuelensis eggs and larvae. Rev Inst Med Trop Sao Paulo. 2017 Apr 3;59:e7. doi: 10.1590/S1678-9946201759007. PMID: 28380118; PMCID: PMC5441158.

Maslinic Acid

Parasitostatic effect of maslinic acid. I. Growth arrest of Plasmodium falciparum intraerythrocytic stages

Abstract

Background: Natural products have played an important role as leads for the development of new drugs against malaria. Recent studies have shown that maslinic acid (MA), a natural triterpene obtained from olive pomace, which displays multiple biological and antimicrobial activities, also exerts inhibitory effects on the development of some Apicomplexan, including Eimeria, Toxoplasma and Neospora. To ascertain if MA displays anti-malarial activity, the main objective of this study was to asses the effect of MA on Plasmodium falciparum-infected erythrocytes in vitro.

Methods: Synchronized P. falciparum-infected erythrocyte cultures were incubated under different conditions with MA, and compared to chloroquine and atovaquone treated cultures. The effects on parasite growth were determined by monitoring the parasitemia and the accumulation of the different infective stages visualized in thin blood smears.

Results: MA inhibits the growth of P. falciparum Dd2 and 3D7 strains in infected erythrocytes in, dose-dependent manner, leading to the accumulation of immature forms at IC50 concentrations, while higher doses produced non-viable parasite cells. MA-treated infected-erythrocyte cultures were compared to those treated with chloroquine or atovaquone, showing significant differences in the pattern of accumulation of parasitic stages. Transient MA treatment at different parasite stages showed that the compound targeted intra-erythrocytic processes from early-ring to schizont stage. These results indicate that MA has a parasitostatic effect, which does not inactivate permanently P. falciparum, as the removal of the compound allowed the infection to continue.

Conclusions: MA displays anti-malarial activity at multiple intraerythrocytic stages of the parasite and, depending on the dose and incubation time, behaves as a plasmodial parasitostatic compound. This novel parasitostatic effect appears to be unrelated to previous mechanisms proposed for current anti-malarial drugs, and may be relevant to uncover new prospective plasmodial targets and opens novel possibilities of therapies associated to host immune response.

Source: Moneriz, C., Marín-García, P., García-Granados, A. et al. Parasitostatic effect of maslinic acid. I. Growth arrest of Plasmodium falciparum intraerythrocytic stages. Malar J 10, 82 (2011). https://doi.org/10.1186/1475-2875-10-82

Turmeric

Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were “turmeric,” “curcuma,” “curcumin,” “arthritis,” and “osteoarthritis.” A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: −2.04 [−2.85, −1.24]) with turmeric/curcumin in comparison with placebo (P < .00001), whereas meta-analysis of four studies showed a decrease of WOMAC with turmeric/curcumin treatment (mean difference: −15.36 [−26.9, −3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy of turmeric for arthritis.

Source: Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016 Aug;19(8):717-29. doi: 10.1089/jmf.2016.3705. PMID: 27533649; PMCID: PMC5003001.

Curcumin and Diabetes: A Systematic Review

Abstract

Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications of curcumin for glycemia and diabetes-related liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular diseases, pancreatic disorders, and other complications, and we also discuss its antioxidant and anti-inflammatory properties. The applications of additional curcuminoid compounds for diabetes prevention and treatment are also included in this paper. Finally, we mention the approaches that are currently being sought to generate a “super curcumin” through improvement of the bioavailability to bring this promising natural product to the forefront of diabetes therapeutics.

Source: Zhang DW, Fu M, Gao SH, Liu JL. Curcumin and diabetes: a systematic review. Evid Based Complement Alternat Med. 2013;2013:636053. doi: 10.1155/2013/636053. Epub 2013 Nov 24. PMID: 24348712; PMCID: PMC3857752.

Onion Extract

Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae

Abstract

Background: Garlics and onions have been used for the treatment of diseases caused by parasites and microbes since ancient times. Trypanosomiasis and leishmaniasis are a concern in many areas of the world, especially in poor countries.

Methods: Trypanosoma brucei brucei and Leishmania tarentolae were used to investigate the anti-parasitic effects of dichloromethane extracts of Allium sativum (garlic) and Allium cepa (onion) bulbs. As a confirmation of known antimicrobial activities, they were studied against a selection of G-negative, G-positive bacteria and two fungi. Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (LC-ESI-MS/MS).

Results: Chemical analyses confirmed the abundance of several sulfur secondary metabolites in garlic and one (zwiebelane) in the onion extract. Both extracts killed both types of parasites efficiently and inhibited the Trypanosoma brucei trypanothione reductase irreversibly. In addition, garlic extract decreased the mitochondrial membrane potential in trypanosomes. Garlic killed the fungi C. albicans and C. parapsilosis more effectively than the positive control. The combinations of garlic and onion with common trypanocidal and leishmanicidal drugs resulted in a synergistic or additive effect in 50% of cases.

Conclusion: The mechanism for biological activity of garlic and onion appears to be related to the amount and the profile of sulfur-containing compounds. It is most likely that vital substances inside the parasitic cell, like trypanothione reductase, are inhibited through disulfide bond formation between SH groups of vital redox compounds and sulfur-containing secondary metabolites.

Source: Krstin S, Sobeh M, Braun MS, Wink M. Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae. Medicines (Basel). 2018 Apr 21;5(2):37. doi: 10.3390/medicines5020037. PMID: 29690511; PMCID: PMC6023319.

The Role of Onion (Allium cepa) in Controlling Parasitic Diseases: a Mini Review

Abstract

Parasitic infection is not one of the major challenges of developing countries. Despite extensive research, finding an effective strategy to combat parasites still requires more knowledge. The appearance of drug resistance in parasite strains and the growing side effects of chemical drugs have raised the use of medicinal plants as antiparasitic agents in recent years. Onion is one of the advantageous vegetables whose role in restricting the growth of certain parasites has been confirmed in numerous studies. It has been attempted in the present review article to discuss the antiparasitic effects of onions and their derivatives by reviewing recent studies.

Source: Cheraghipour, Kourosh & Marzban, A. & Ezatpour, Behrouz & Nazarabad, Vahideh. (2020). The Role of Onion (Allium cepa) in Controlling Parasitic Diseases: a Mini Review.

A review of anti-inflammatory, antioxidant, and immunomodulatory effects of Allium cepa and its main constituents

Abstract

Context: Allium cepa L. (Liliaceae), known as onion, is consumed throughout the world. Onion and its derivatives including saponins, aglycones, quercetin, cepaenes, flavonoids, organosulfurs, and phenolic compounds, showed various pharmacological properties and therapeutic effects.

Objective: Anti-inflammatory, antioxidant, and immunomodulatory effects of A. cepa and its main constituents, along with the underlying molecular mechanisms are presented.

Methods: Databases including, Web of Knowledge, Medline/PubMed, Scopus, and Google Scholar were checked for articles published between 1996 and the end of July 2020, using the key-words Allium cepa, quercetin, anti-inflammatory, antioxidant and immunomodulatory.

Results: A. cepa and its constituents mainly quercetin showed anti-inflammatory effects mediated via reduction of total and differential WBC counts, inhibition of chemotaxis of polymorphonuclear leukocytes, COX, and LOX pathways and prevented formation of leukotrienes and thromboxanes, prostaglandin E2 (PGE2) as onVCAM-1, NF-κB, MARK,d STAT-1, JNK, p38 and osteoclastogenesis. A. cepa and its derivatives showed antioxidant effect by decreasing lipid peroxidation, NAD(P)H, MDA, NO, LPO and eNOS but enhancing antioxidants such as SOD, CAT, GSH, GPx, GSPO, TrxR, SDH, GST and GR activities and thiol level. Immunomodulatory effects of the plant and quercetin was also shown by reduction of Th2 cytokines, IL-4, IL-5, and IL-13 as well as IL-6, IL-8, IL-10, IL-1β and TNF-α and IgE levels, but increased CD4 cells, IFN-γ level and IFN-γ/IL4 ratio (Th1/Th2 balance).

Conclusions: The effect of onion and its constituents on oxidative stress, inflammatory and immune system were shown indicating their therapeutic value in treatment of various diseases associated with oxidative stress, inflammation, and immune-dysregulation.

Source: Marefati N, Ghorani V, Shakeri F, Boskabady M, Kianian F, Rezaee R, Boskabady MH. A review of anti-inflammatory, antioxidant, and immunomodulatory effects of Allium cepa and its main constituents. Pharm Biol. 2021 Dec;59(1):287-302. doi: 10.1080/13880209.2021.1874028. PMID: 33645419; PMCID: PMC7919894.

Piperine

Anti-inflammatory activity of piperine

Abstract

Piperine (1-peperoyl piperidine) was isolated from Piper nigrum Linn for the evaluation of anti-inflammatory activity in rats. Different acute and chronic experimental models like carrageenin-induced rat paw edema, cotton pellet granuloma, and croton oil-induced granuloma pouch, were employed. Simultaneously, biochemical estimations were made to elucidate the underlying mechanism of the action. Piperine acted significantly on early acute changes in inflammatory processes and chronic granulative changes. It also acted partially through stimulation of pituitary adrenal axis. Exudative changes in both acute and chronic models, however, were insignificant.

Source: Mujumdar AM, Dhuley JN, Deshmukh VK, Raman PH, Naik SR. Anti-inflammatory activity of piperine. Jpn J Med Sci Biol. 1990 Jun;43(3):95-100. doi: 10.7883/yoken1952.43.95. PMID: 2283727.

The antioxidant and radical scavenging activities of black pepper (Piper nigrum) seeds

Abstract

Water and ethanol crude extracts from black pepper (Piper nigrum) were investigated for their antioxidant and radical scavenging activities in six different assay, namely, total antioxidant activity, reducing power, 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. Both water extract (WEBP) and ethanol extract (EEBP) of black pepper exhibited strong total antioxidant activity. The 75 microg/ml concentration of WEBP and EEBP showed 95.5% and 93.3% inhibition on peroxidation of linoleic acid emulsion, respectively. On the other hand, at the same concentration, standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and alpha-tocopherol exhibited 92.1%, 95.0%, and 70.4% inhibition on peroxidation of linoleic acid emulsion, respectively. Also, total phenolic content in both WEBP and EEBP were determined as gallic acid equivalents. The total phenolics content of water and ethanol extracts were determined by the Folin-Ciocalteu procedure and 54.3 and 42.8 microg gallic acid equivalent of phenols was detected in 1 mg WEBP and EEBP.

Source: Gülçin I. The antioxidant and radical scavenging activities of black pepper (Piper nigrum) seeds. Int J Food Sci Nutr. 2005 Nov;56(7):491-9. doi: 10.1080/09637480500450248. PMID: 16503560.

Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers

Abstract

Piperine is the principal alkaloid in black peppers (Piper nigrum L.), which is a commonly included spice in anti-diarrheal formulations. Piperine has antispasmodic activities, but its anti-secretory effect is not known. Therefore, this study investigated the anti-secretory effect of piperine and its underlying mechanism. Piperine inhibited cAMP-mediated Cl− secretion in human intestinal epithelial (T84) cells, similar to black pepper extract. Intraluminal administration of piperine (2 μg/loop) suppressed cholera toxin-induced intestinal fluid accumulation by ∼85% in mice. The anti-secretory mechanism of piperine was investigated by evaluating its effects on the activity of transport proteins involved in cAMP-mediated Cl− secretion. Notably, piperine inhibited CFTR Cl− channel activity (IC50#8’6#10 μM) without affecting intracellular cAMP levels. The mechanisms of piperine-induced CFTR inhibition did not involve MRP4-mediated cAMP efflux, AMPK or TRPV1. Piperine also inhibited cAMP-activated basolateral K+ channels, but it had no effect on Na+–K+–Cl− cotransporters or Na+–K+ ATPases. Piperine suppressed Ca2+-activated Cl− channels (CaCC) without affecting intracellular Ca2+ concentrations or Ca2+-activated basolateral K+ channels. Collectively, this study indicates that the anti-secretory effect of piperine involves the inhibition of CFTR, CaCC and cAMP-activated basolateral K+ channels. Piperine represents a novel class of drug candidates for the treatment of diarrheal diseases caused by the intestinal hypersecretion of Cl−.

Source: Pawin Pongkorpsakol, Preedajit Wongkrasant, Saowanee Kumpun, Varanuj Chatsudthipong, Chatchai Muanprasat, Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers, Pharmacological Research, Volume 100, 2015, Pages 271-280, ISSN 1043-6618, https://doi.org/10.1016/j.phrs.2015.08.012.

Pharmacological Basis for the Medicinal Use of Black Pepper and Piperine in Gastrointestinal Disorders

Abstract

Dried fruits of Piper nigrum (black pepper) are commonly used in gastrointestinal disorders. The aim of this study was to rationalize the medicinal use of pepper and its principal alkaloid, piperine, in constipation and diarrhea using in vitro and in vivo assays. When tested in isolated guinea pig ileum, the crude extract of pepper (Pn.Cr) (1–10 mg/mL) and piperine (3–300 μM) caused a concentration-dependent and atropine-sensitive stimulant effect. In rabbit jejunum, Pn.Cr (0.01–3.0 mg/mL) and piperine (30–1,000 μM) relaxed spontaneous contractions, similar to loperamide and nifedipine. The relaxant effect of Pn.Cr and piperine was partially inhibited in the presence of naloxone (1 μM) similar to that of loperamide, suggesting the naloxone-sensitive effect in addition to the Ca(2+) channel blocking (CCB)-like activity, which was evident by its relaxant effect on K+ (80 mM)-induced contractions. The CCB activity was confirmed when pretreatment of the tissue with Pn.Cr (0.03–0.3 mg/mL) or piperine (10–100 μM) caused a rightward shift in the concentration–response curves of Ca(2+), similar to loperamide and nifedipine. In mice, Pn.Cr and piperine exhibited a partially atropine-sensitive laxative effect at lower doses, whereas at higher doses it caused antisecretory and antidiarrheal activities that were partially inhibited in mice pretreated with naloxone (1.5 mg/kg), similar to loperamide. This study illustrates the presence of spasmodic (cholinergic) and antispasmodic (opioid agonist and Ca(2+) antagonist) effects, thus providing the possible explanation for the medicinal use of pepper and piperine in gastrointestinal motility disorders.

Source: Mehmood, Malik Hassan & Gilani, Anwar-ul. (2010). Pharmacological Basis for the Medicinal Use of Black Pepper and Piperine in Gastrointestinal Disorders. Journal of medicinal food. 13. 1086-96. 10.1089/jmf.2010.1065.

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