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Phyto-pharmacological review on bioavailability enhancer [Trikatu]
Background
The concept of bioenhancer comes from Ayurveda. Many ways have been documented in the literature to boost the bioavailability of poorly bioavailable medications, and one of the most recent techniques is the use of bioavailability enhancers.
Main body of the abstract
Herbal bioenhancers are a choice of bioenhancer in modern medicine because of their easy absorption, safety, and lack of side effects. They also reduce drug toxicity, decrease treatment times, and lower treatment costs. Increasing drug bioavailability after oral administration is medically relevant since bioavailability has a direct impact on plasma drug concentrations and therapeutic bioefficacy. When medicine is coupled with a suitable bioenhancer, the bioavailability of the drug is increased. The drug and bioenhancers have no synergistic effect. They reduce the dosage, cost, toxicity, and other side effects, as well as the amount of time it takes to act.
Short conclusion
The objective of these survey is that to investigate the thought of the bioavailability to get a superior therapeutic response within the right portion with natural pharmaceuticals containing product, as well as the classification of bioenhancers, mechanism of action, commercial formulation, and future prospects.
Medical devices made of substances (MDMS) have recently gained great popularity in several specialties of internal medicine, including gastroenterology. In the last decades this discipline has known relevant advances in the cure of severe diseases, such as peptic ulcer, gastroesophageal reflux disease and chronic hepatitis C, thanks to the revolutionary development of new drugs able to act on single receptors changing a particular cell function or blocking microbial and viral replication. However, there are many gastroenterological illnesses that are difficult to treat with traditional medicinal products because of their complex and poorly known pathophysiology, which comprises altered motility, visceral hypersensitivity, gut dysbiosis, intestinal mild inflammation with impaired immune function, increased mucosal permeability and abnormal brain-gut interaction. They are mainly represented by esophageal functional disorders (reflux hypersensitivity, functional heartburn), functional dyspepsia, irritable bowel syndrome, functional constipation and functional diarrhea. Traditional drugs do not provide a definitive resolution of these disorders with a multifactorial pathogenesis and they can benefit from the use of MDMS, which seem to have the ability to act on different factors thanks to the synergistic action of their various components. International medical literature already reports many clinical trials performed with the well-known standards for evaluating their efficacy and safety in a great part of the above-mentioned conditions.
Gingers is widely used as the complimentary household herbal medicine since it promotes varieties of health-protective effects including anti-hyperlipidemia and anti-hypertension. This study aimed to evaluate the effect of a 30-day ginger (Zingiber officinale Roscoe, Zingiberaceae) ingestion on lipid and glucose profiles and blood pressures in hypertensive older women. The randomized double-blinded ginger consumption was designed in normotensive and hypertensive older women. Thirty-two female volunteers were randomly allocated into 4 groups of normotensives and hypertensives without and with ginger consumption, named as normotensive control (NC); normotensive with ginger consumption (NG); hypertensive control (HC) and hypertensive with ginger consumption (HG). On daily basis, the ginger-treated groups (NG and HG) ingested ginger powder at 75 mg/kgBW/day dissolved in 150 mL water after breakfast whereas control groups (NC and HC) received 150 mL water only for 30 days. Data were collected, in the morning, at pre- and post-intervention. Blood lipids, including cholesterol (chol), triglycerides (TG), high density lipoproteins (HDL), and low density lipoproteins (LDL), glucose levels and blood pressures were evaluated and compared from pre- and post-interventions. The results showed that 30-day ingestion of ginger exerted no change in normotensive groups, where alterations of blood lipid profiles were found in hypertensive groups. Both hypertensive groups (HC and HG) showed the significant reductions in SBP (p < 0.05), however, HC showed significantly increase in blood TG and LDL. HG group showed the reduction in TG and unchanged in LDL. There were no significant differences in chol, HDL, glucose levels and health-related performance from either within or between-groups comparisons (p > 0.05). This study primarily shows the minimal duration of 30-day ingestion of dissolved ginger on lowering systolic blood pressure and triglycerides but plays no roles in glycemic control in hypertensive subjects. Ginger might possibly play an important alternative role in alleviating certain health risks in the hypertensive aged females. To build up confidence on its therapeutic effect, more sample size of this local herb is needed in further investigation. HIGHLIGHTS Ginger is widely reported in traditional medicine to relieve symptoms and certain diseases. This herb is popularly used and easily find in Oriental countries Ginger can be used to minimize the high prevalence of dyslipidemia and hypertension among Thai population, especially in the north and north-east regions The minimum 30 days of ginger ingestion shows some effectiveness on blood lipids and lowers systolic blood pressure in hypertensive elderly Ginger might possibly play additional important roles in alleviating certain health risk in the aged GRAPHICAL ABSTRACT
Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.
Piper longum (family Piperaceae), commonly known as "long-pepper" or "Pippali" grows as a perennial shrub or as an herbaceous vine. It is native to the Indo-Malaya region and widely distributed in the tropical and subtropical world including the Indian subcontinent, Sri Lanka, Middle-East, and America. The fruits are mostly used as culinary spice and preservatives and are also a potent remedy in various traditional medicinal systems against bronchitis, cough, cold, snakebite, and scorpion-sting and are also used as a contraceptive. Various bioactive-phytochemicals including alkaloids, flavonoids, esters, and steroids were identified from the plant extracts and essential oils from the roots and fruits were reported as antimicrobial, antiparasitic, anthelminthic, mosquito-larvicidal, antiinflammatory, analgesic, antioxidant, anticancer, neuro-pharmacological, antihyperglycaemic, hepato-protective, antihyperlipidaemic, antiangiogenic, immunomodulatory, antiarthritic, antiulcer, antiasthmatic, cardioprotective, and anti-snake-venom agents. Many of its pharmacological properties were attributed to its antioxidative and antiinflammatory effects and its ability to modulate a number of signalling pathways and enzymes. This review comprehensively encompasses information on habit, distribution, ethnobotany, phytochemistry, and pharmacology of P. longum in relation to its medicinal importance and health benefits to validate the traditional claims supported by specific scientific experiments. In addition, it also discusses the safety and toxicity studies, application of green synthesis and nanotechnology as well as clinical trials performed with the plant also elucidating research gaps and future perspectives of its multifaceted uses.
Stability study of the Ayurvedic formulations plays a significant role to provide actual shelf life of the medicament. Hence, it is necessary to perform stability studies of Ayurvedic compound formulations. The stability study was planned to observe whether any physical, chemical, and microbiological change takes place in Vyaghri Haritaki samples by keeping them at three different temperatures (47°C, 37°C, and 25-30°C) for 3 months. The samples kept for accelerated stability study were analyzed after 3 months and the details have been presented in this section.
Background
Ionizing radiations causes harm to living organisms and the rapid technological progress has increased human exposure to ionizing radiations enormously. Ionizing radiations come in contact with exposure from space radiations, nuclear war, and radiotherapy for cancer-like disease.
Main body of the abstract
There is a need for human beings against these effects of ionizing radiation due to lack of safe and effective radiation available so far, and the traditional medicines used from ancient times of different disease and protection against radiation. A systematic in vivo and in vitro study may use to identify a new lead compound as a radiation shielding agent. The radioprotective properties of plant and herbal extracts, as well as their radioprotective doses, are highlighted in this article. The outcomes of the in vitro and in vivo studies indicate that several botanicals such as Gingko biloba, Centella asiatica, Ocimum sanctum, Panax ginseng, Emblica officinalis, Phyllanthus amarus, Piper longum, Tinospora cordifoila, Mentha arvensis, Mentha piperita, Syzygium cumini, Zingiber officinale, Ageratum conyzoides, Aegle marmelos and Piper betle protect against radiation-induced lethality, lipid peroxidation, and DNA damage.
Short conclusion
The fractionation-guided evaluation may help to develop new radioprotectors for targeted activities.
Science of Marma known as Marma Vigyanam is a dynamic part, specially described in Sushrut samhita and other Ayurvedic classics. According to Sushrut Mamsa, Sira, Snayu, Asthi, and Sandhi, these five elements collectively present at Marma point. This is the peculiarity of Marma.1 Marmas are the vital points on the body having importance regarding surgical procedure and traumatic effect. It is also known as Ayurvedic Accupressure. In this paper, three similar cases of pain and stiffness in shoulder joints are presented, who has attended OPD of District Hospital Shivaji Nagar, Bhopal. In during the clinical examination partially restriction of shoulder movement is also recorded. The case was initially treated with Marma therapy mainly the stimulation of bilateral Bahu Marma along withAmsa Marma for instant pain management. After the treatment of about ten minutes the patient got relief in pain and stiffness and felt lightness in surrounding area of painful place. Amsa Marma manipulation can be used to give instant relief from Shoulder pain effectively.
Among the large number of plants that are part of the Ayurvedic system of medicine in India and Bangladesh, Zingiber officinale Roscoe (Zingiberaceae), or ginger in English, holds a special place and is often referred to as “Mahaushadha” (great medicine) and “Vishvabhesaja” (worldwide or universal herb) to signify its special status. The plant and particularly its rhizomes are used both in the raw and dry form for the relief of a multitude of disorders. Since a number of these disorders occur in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it was of interest to perform in silico studies (molecular docking) to evaluate the binding affinities of a number of constituents of Zingiber officinale with the 3C-like protease or main protease (Mpro) of SARS-CoV-2, which plays an essential role in the cleavage of viral polyproteins and subsequent viral replication. Our studies indicated that 2 of the compounds present in ginger, namely, chlorogenic acid and hesperidin, had high binding affinities for Mpro with predicted binding energies of −7.5 and −8.3 kcal/mol. The two-dimensional and three-dimensional interactions also showed that, while chlorogenic acid interacts with one of the His41 amino acids of the catalytic dyad of Mpro, hesperidin interacts with the other amino acid Cys145, which can account for their predicted high binding energies and, therefore, possibly can inhibit Mpro activity. Taken together, our findings indicate that ginger, besides alleviating the symptoms induced by SARS-CoV-2, may also play a role in inhibiting the virus.
Plants and their extracts have traditionally been used against various pathologies and in some regions are the only therapeutic source for the treatment and prevention of many chronic diseases [...]
Background: Black pepper [Piper nigrum (L.), Family: Piperaceae] is used traditionally for the treatment of various diseases including; cough, cold, dyspnea throat diseases, intermittent fever, dysentery, stomachache, worms and piles. The pharmacological potential of black pepper is due to the presence of metabolites like phenolic compounds, alkaloids, flavonoids, carotenoids, terpenoids, etc. The multipurpose use of black pepper dried seeds has several other beneficial health effects that also received in the light of traditional as well as current medicine perspectives. The review aims to discuss the botany, phytochemical constituents, and pharmacological properties of piperine and black pepper essential oil (BPEO).
Results: Phytochemical analyses have described the main chemical constituents of black pepper, including carbohydrates, proteins, calcium, magnesium, potassium, iron, vitamin C, tannins, flavonoids and carotenoids. The volatile oil content ranges from 0.4 to 7 % in dried berries. The major constituents of BPEO are sabinene, 3-carene,
D-limonene, α-pinene, caryophyllene, β-phellandrene, α-phellandrene, α-thujene, and β-bisabolene. Additionally, piperine is the naturally occurring and principal bioactive alkaloid constituent of black pepper owing to its potential therapeutic properties, including cerebral brain functioning and increased nutrient absorption. The BPEO has several
biological roles, including antioxidant, anti-inflammatory, anticancer, anti-obesity, antidepressant, antidiabetic, antimicrobial, gastroprotective, and insecticidal activities.
Conclusions: This review examines and presents the appropriate evidence on black pepper and its traditional uses as well as biological activities of BPEO and piperine. Although several previous reports
showed diverse biological effects for piperine and bioactive constitutes of BPEO. Thus, minimal investigations were conducted using animal models, and many of these studies also lacked appropriate experimental setting like doses, control details. Hence, future studies are necessary to understand the mechanism of piperine, BPEO, bioactive constituents and their effects upon their use by animal models and humans with the proper experimental procedure which we can facilitate the protection of human health
from several diseases.
Ayurveda has mentioned so many formulations on different diseases. Each formulation is having Ras, Guna, Veerya and Vipaka as its properties. According to that properties, mode of action of that particular formulation, can be determined in that particular disease. Trikatu is one of them, it contains three herbal drugs i.e. Sunthi (Zinziber officinalis), Marich (Piper nigram), and Pippali (Piper longum). It acts mainly on Shwas (Asthma), Prameha (Diabetes), Twak roga (Skin diseases), Sleepad (Elephantitis), Medoroga (Obesity), and Pinas (Rhinitis). Trikatu acts only in specific situation of dosha dominating. Also, Trikatu is adtableded in many Ayurvedic polyherbal formulations in such a quantity that it will be sufficient to enhance the bioavailability of the main ingredients of that formulation by acting through various mechanisms.
This article brings together an overview of the historical and scientific works on black pepper (BP). It's well known as the king of spices, and literature which is very rich showing that it was well cultivated tens of centuries ago before the birth of Christ. It was known first in India but its economic importance as well as medical uses extended to several countries. The ancient books illustrated the displacements of caravans of merchants known as route of Silks and Spices. Actually, the countries of India, Brazil, and Indonesia are the greatest commercial exporters. The major compound of black pepper is piperine that imparts pungency and biting taste to it. Hundreds of millions of results on black pepper on Google reflects the importance of this naturally occurring alkaloid. The numerous health effects and beneficial therapeutic properties have been largely demonstrated. The chemical composition of BP is so various to find heterocyclic components, and mineral ions as potassium, calcium, magnesium, iron … Advanced extraction and quick characterization yield these numerous alkaloids based on piperine. Also, the development of new formulations improves its in vivo bioavailability and explains the multiple uses of this "King" of spices in the medicinal applications. Black pepper and its isolated compounds served also as efficient corrosion of mild steel in acidic media
Purpose
To evaluate the efficacy of a new food-grade lecithin formulation of standardized extracts of Zingiber officinale and Acmella oleracea on pain and inflammation.
Patients and Methods
Pilot study with one-group pretest–posttest quasi-experimental design in which 50 subjects with moderate knee osteoarthritis (OA) (mean age: 62.46±8.45) were supplied for four weeks with two tablets/day.
Results
Primary outcomes were 1) the evaluation of pain intensity, by a 30-day visual analogue scale (VAS) and 2) the assessment of knee function by WOMAC (Western Ontario and McMaster Universities Arthritis) Index and by Tegner Lysholm Knee Scoring collected at baseline, at 15 and 30 days after treatment. Secondary outcomes were 3) health-related quality of life, by the ShortForm36 (SF-36); 4) inflammation grade by C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR); and 5) body composition by dual-energy X-ray absorptiometry (DXA) measured at baseline and 30 days after treatment. Data showed significant effects of supplement intake for WOMAC (β=−3.27, p<0.0001), Lysholm (β=1.06, p=0.0003), CRP (β=−0.13, p=0.006), ESR (β=−3.09, p=0.004), physical activity (β=4.3, p=0.009) and fat-free mass (β=376.7, p=0.046). A significant VAS’s decrease over time was observed in both knees (left: β=−0.08, p<0.0001; right: β=−0.07, p<0.0001).
Conclusion
The tested formulation seems to be effective and also free of side effects.
Earthen hemisphere is gifted with varieties of large number of medicinal herbs. Herbs are natural remedies for the disease with higher safety profile and efficacy. India has an ancient heritage of traditional herbal medicine. Ayurvedic literature has a treasure of medicinal herbs in which Trikatu is very important drug. Trikatu is used as solo drug rarely, but it is an essential ingredient of numerous formulations and prescriptions of Ayurvedic medicine. Trikatu is a poly herbal preparation, It consists of three crude drugs namely maricha (Piper nigrum Linn.), Pippali (Piper longum Linn.) and Shunthi (Zingiber officinalis Rosc) in the ratio of (1:1:1; w:w). Trikatu curna is considered as one of the best drugs to treat the condition of Ama(improperly digested absorbed and improperly metabolised food particles including free radicles) . Trikatu is regarded as the drug of choice in cases of Agnimandya (poor digestion due to faulty digestive process). In Brihattrayi, it is recommended for various diseases due to Agni (digestive fire) vitiation such as Grahaniroga(Malabsorbtion syndrome), Udara roga(major diseases of abdomen surgical and medical like hepatomegaly, spleenomegaly and ascitis ), Arsharoga(piles) etc. The objective of this article is to highlight classification, synonyms, pharmacological actions as described in various diseases, and different formulations of Trikatu in ancient Ayurvedic literature in special reference of Brihattrayi and Nighantus.
Maximizing oral bioavailability is therapeutically important because the extent of bioavailability directly influences plasma concentrations and therapeutic efficacy after oral drug administration. Bioavailability of poor bioavailable drugs can be increased from the many available approaches in the literature and the most recent approach is the use of bioavailability enhancers. The use of bioenhancers seems to be a fruitful method for increasing bioavailability of an orally administered drug and nutraceutical. This approach leads to improved formulation with enhanced oral bioavailability of the active ingredient. Bioenhancers constitute an innovative concept and judicious use of bioenhancers lead to reductions in drug cost, toxicity, and other adverse effects, and have a beneficial influence on the national economy. This patent review article classifies and describes the various bioenhancers and emphasizes their diverse mechanism of action by virtue of which they act as bioenhancers.
Single crystalline perovskites exhibit high optical absorption, long carrier lifetime, large carrier mobility, low trap-state-density and high defect tolerance. Unfortunately, all single crystalline perovskites attained so far are limited to bulk single crystals and small area wafers. As such, it is impossible to design highly demanded flexible single-crystalline electronics and wearable devices including displays, touch sensing devices, transistors, etc. Herein we report a method of induced peripheral crystallization to prepare large area flexible single-crystalline membrane (SCM) of phenylethylamine lead iodide (C6H5C2H4NH3)2PbI4 with area exceeding 2500 mm² and thinness as little as 0.6 μm. The ultrathin flexible SCM exhibits ultralow defect density, superior uniformity and long-term stability. Using the superior ultrathin membrane, a series of flexible photosensors were designed and fabricated to exhibit very high external quantum efficiency of 26530%, responsivity of 98.17 A W⁻¹ and detectivity as much as 1.62 × 10¹⁵ cm Hz1/2 W⁻¹ (Jones).
Trikatu, as per Ayurveda’s Bhaisajyaratnawali is a compound herbal formulation containing three bitter herbs mixed together in equal quantities. Dried fruits of Piper nigrum (Maricha) and Piper longum (Peepli) and dried rhizomes of Zingiber officinale (Sunthi) are used to prepare this miraculous formulation. It is prescribed in Ayurvedic system of medicine for treatment of tastelessness, digestive impairment, and diseases of nose and throat such as chronic rhinitis/sinusitis, skin diseases, asthma, cough, frequent urination, obesity, and Filariasis. Trikatu is also added in various Ayurvedic formulations with a view to restore the disturbed “tridoshas- vatta, pitta and kapha.” It calms down the increased Vata and Kapha and increases the Pitta. It has pungent (katu) taste, hot (ushna) potency, light (laghu) and dry (ruksha) quality, and digestive (amapachaka) therapeutic effect. Modern pharmacological studies also revealed that Trikatu possesses the capability to enhance the bioavailability of various phytoconstituents and synthetic drugs if incorporated with them thereby helping in achieving the therapeutic goals. Apart from traditionally known health benefits, Trikatu also possesses immunomodulatory, antiviral, expectorant, carminative, hypolipidemic, hypoglycemic, antiemetic, and anti-inflammatory potential. Simply it is concluded that Trikatu is a miraculous combination which is needed to be explored more exhaustively to solve the bioavailability issues of allopathic, ayurvedic, and other traditional systems of medicines.
Different dosage forms (Avaleha, Arishta and Ghrita) of Vasa (Adhatoda vasica Ness.) are recommended to treat Tamaka Shwasa (Bronchial Asthma). These formulations were prepared by keeping the ingredients same to evaluate their efficacy in Tamaka Shwasa (Bronchial Asthma). With this aim, a clinical study was undertaken on Vasa Avaleha, Vasa Arishta and Vasa Ghrita. All these drugs were given two times a day orally for 30 days; it is an open trail with 15 days follow-up. The present study reveals that Vasa Avaleha (p<0.001) and Vasa Arishta (p<0.05) showed highly significant results in frequency and intensity of dyspnoea. While Vasa Ghrita showed statistically insignificant (p>0.05) results. Vasa Avaleha and Vasa Arishta showed statistically significant (p<0.01 and p<0.01 respectively) results in Sakapha Kasa (Productive Cough). On analyzing the overall effect, it was observed that in Avaleha group 77.77 % patient showed moderate improvement while marked improvement is seen in 11% patient followed by Vasa Arishta (33.33%). .
Skin is considered to be the largest and fastest-growing organ in Human body and plays an important role in providing protection from
pathogens and environmental factors. Due to its large surface area, skin is susceptible to a variety of conditions including acne, dermatitis,
eczema, psoriasis, rashes, cellulitis and rosacea. External factors such as skin care products, exogenous chemicals, and the weather can influence
the skin from outside while the food and medicines consumed by individuals can lead to the development of skin disorders from inside the body.
Although there are numerous products on the market for skin conditions and skin health and beauty, active research and development for potent
remedies are still ongoing. An efficient strategy to enhance the efficacy of skin care products and improve their bioavailability and provide longlasting
effect is employment of encapsulation systems such as liposomes and nano liposomes. Here a summary of methods to enhance the efficacy
and bioavailability of skin care ingredients is presented.
The concept of bioavailability enhancer is new to the modern system of medicine. Basically, this concept originated in Ayurveda and being used in this system of medicine since centuries. Bio-enhancers augment the bioavailability or biological activity of drugs when co-administered with principal drug at low doses. Ayurveda is using several drugs such as Piper longum Linn., Zingiber officinale Rosc., and Glycyrhhiza glabra Linn. as bio-enhancers and different methods for bio-enhancing since centuries. The bio-enhancement leads to reduction in therapeutic dose of principal drug, thus reducing the possibilities of toxicity and side effects of drug, potentiating the efficacy, reducing the resistance, decreasing the requirement of raw material for drug manufacture, and ultimately benefitting to the world economy by reducing the treatment cost. This review article attempts to consolidate different drugs as well as methods being used traditionally for enhancing bioavailability in Ayurvedic system of medicine and to discuss their possible mechanism of action. Authentic subject material has been reviewed from different Ayurvedic texts and from different related research and review articles. Thus, it is a humble effort to explore the different aspects of bio-enhancers including therapeutic techniques such as Shodhana, the drugs such as Pippali, and properties such as Yogavahi and Rasayana, which have been described in Ayurveda along with their mechanism of action and uses wherever available.
Epilepsy has 2-3% incidence worldwide. However, present antiepileptic drugs provide only partial control of seizures. Calcium ion accumulation in hippocampal neurons has long been known as a major contributor to the etiology of epilepsy. TRPV1 is a calcium-permeable channel and mediator of epilepsy in the hippocampus. TRPV1 is expressed in epileptic brain areas such as CA1 area and dentate gyrus of the hippocampus. Here the author reviews the patent literature on novel molecules targeting TRPV1 that are currently being investigated in the laboratory and are candidates for future clinical evaluation in the management of epilepsy.
A limited number of recent reports have implicated TRPV1 in the induction or treatment of epilepsy suggesting that this may be new area for potential drugs targeting this debilitating disease. Thus activation of TRPV1 by oxidative stress, resiniferatoxin, cannabinoid receptor (CB1) activators (i.e. anandamide) or capsaicin induced epileptic effects, and these effects could be reduced by appropriate inhibitors, including capsazepine (CPZ), 5'-iodoresiniferatoxin (IRTX), resolvins, and CB1 antagonists. It has been also reported that CPZ and IRTX reduced spontaneous excitatory synaptic transmission through modulation of glutaminergic systems and desensitization of TRPV1 channels in the hippocampus of rats. Immunocytochemical studies indicated that TRPV1 channel expression increased in the hippocampus of mice and patients with temporal lobe epilepsy
Taken together, findings in the current literature support a role for calcium ion accumulation through TRPV1 channels in the etiology of epileptic seizures, indicating that inhibition of TRPV1 in the hippocampus may possibly be a novel target for prevention of epileptic seizures.
Medicinal plants are very popular in different traditional systems of medicines due to their diverse
pharmacological potentials and lesser side effects in biological systems. Piper nigrum L. (Family Piperaceae)
is a well known spice considered as ‘‘The King of spices’’ among various spices. It contains a pungent alkaloid
‘‘piperine’’ which is known to possess many pharmacological actions. Piperine increases bioavailability of
many drugs and nutrients by inhibiting various metabolising enzymes. Piper nigrum L and its active constituent
‘’Piperine’’exhibits diverse pharmacological activities like antihypertensive, antiplatelet, antioxidant, antitumor,
anti-asthmatics, analgesic, anti-inflammatory, anti-diarrheal, antispasmodic, antidepressants, immunomodulatory, anticonvulsant, anti-thyroids, antibacterial, antifungal, hepato-protective, insecticidal and larvicidal activities etc. The current review article is aimed to provide an updated literature review on recent advancement of pharmacognosy, chemistry and pharmacological activities of Piper nigrum L.
Background
Currently chemotherapy is limited mostly to genotoxic drugs that are associated with severe side effects due to non-selective targeting of normal tissue. Natural products play a significant role in the development of most chemotherapeutic agents, with 74.8% of all available chemotherapy being derived from natural products.
Objective
To scientifically assess and validate the anticancer potential of an ethanolic extract of the fruit of the Long pepper (PLX), a plant of the piperaceae family that has been used in traditional medicine, especially Ayurveda and investigate the anticancer mechanism of action of PLX against cancer cells.
Materials & Methods
Following treatment with ethanolic long pepper extract, cell viability was assessed using a water-soluble tetrazolium salt; apoptosis induction was observed following nuclear staining by Hoechst, binding of annexin V to the externalized phosphatidyl serine and phase contrast microscopy. Image-based cytometry was used to detect the effect of long pepper extract on the production of reactive oxygen species and the dissipation of the mitochondrial membrane potential following Tetramethylrhodamine or 5,5,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine chloride staining (JC-1). Assessment of PLX in-vivo was carried out using Balb/C mice (toxicity) and CD-1 nu/nu immunocompromised mice (efficacy). HPLC analysis enabled detection of some primary compounds present within our long pepper extract.
Results
Our results indicated that an ethanolic long pepper extract selectively induces caspase-independent apoptosis in cancer cells, without affecting non-cancerous cells, by targeting the mitochondria, leading to dissipation of the mitochondrial membrane potential and increase in ROS production. Release of the AIF and endonuclease G from isolated mitochondria confirms the mitochondria as a potential target of long pepper. The efficacy of PLX in in-vivo studies indicates that oral administration is able to halt the growth of colon cancer tumors in immunocompromised mice, with no associated toxicity. These results demonstrate the potentially safe and non-toxic alternative that is long pepper extract for cancer therapy.
Ginger (Zingiber officinale) belonging to the family Zingiberaceae is a perennial herb. It is widely distributed in tropical Asia. In India, it is cultivated mainly in Kerala, Andhia Pradesh, Uttar Pradesh, West Bengal and Maharashtra. It is one of the most common spices, which is in use since centuries for its versatile medicinal actions like antiemetic, stomachic, expectorant, anti-inflammatory, aphrodisiac etc in traditional system of medicine (Unani, Ayurveda, and Chinese medicine). It is useful for the treatment of various gastrointestinal, pulmonary, cardiovascular and sexual disorders. The phytochemical study of ginger showed the presence of many volatile oils and oleo-resins like gingerol, zinger one, zingiberol etc. Numerous experimental and clinical trials have proven ginger for its range of therapeutic activities such as antibacterial, antidiabetic, antiemetic, hypolipidaemic, hepatoprotective etc properties. The present article aims to explore traditional Unani and pharmacological activities of this herb reported till date.
Earthen hemisphere is gifted with varieties of large number of medicinal herbs. Herbs are natural remedies for the disease with higher safety profile and efficacy. The country like India has got variety of climatic conditions and seasons favorable for growth of many species of plants. Amongst the large number of herbal drugs existing in India, very few have been studied systematically so far. The list of drugs is very meticulous and diversified hence extensive efforts are required for their correct recognition. Piper longum is a highly valuable drug and is one of the essential ingredients in the most of the compound preparations included in Ayurvedic literature. Further, the use of the plant as a bioavailability enhancer has immensely increased its importance in the field of Ayurveda. Hence, an attempt has been made to address the chemistry and pharmacology of the plant P. longum. Commonly the plant P. longum is known as long pepper, species of the genus Piper belonging to family piperaceae of the unique order piperales of the verticillate of dicotyledones.
Concept of bioenhancers or biopotentiators was first time reported in 1929 by Bose. A bioenhancer is an agent capable of enhancing bioavailability and efficacy of a drug with which it is co-administered, without any pharmacological activity of its own at therapeutic dose used. Development and consequent isolation of these molecules, such as piperine and quercetin, is considered as scientific breakthrough. A fixed drug combination (Risorine) of rifampicin, isoniazid, and piperine is the result of this research. It contains almost 60% less dose of rifampicin because of its increased bioavailability and it also prevents resistance. This concept is mentioned as yogvahi in ayurveda and was used to increase the effect of medicines by increasing oral bioavailability, decreasing adverse effects and to circumvent parenteral routes of drug administration. More such useful and economically viable drug combinations can be developed by integrating knowledge of time tested ayurveda with modern methods of research. This review is an account of these bioenhancers, available from the natural resources.
Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.
The organogenic potential and antioxidant potential (1, 1-diphenyl-2-picrylhydrazyl-scavenging activity) of the medicinal
plant Piper nigrum L. (black pepper) were investigated. Callus induction and shoot regeneration were induced from leaf explants of potted plants
cultured on MS medium supplemented with different plant growth regulators. The best callogenic response was observed on explants
cultured for 30 days on MS medium supplemented with either 0.5or 1.5 mgl−1 6-benzyladenine (BA) + 1.0mgl−1 α-naphthaleneacetic acid. Subsequent transfer of the callogenic explants onto MS medium supplemented with 1.5mgl−1 BA + 1.0mgl−1 gibberellic acid (GA3) achieved 85% shoot organogenesis after 30 days of culture. The maximum number (7.2) of shoots/explant was recorded for explants
cultured in MS medium supplemented with 1.0mgl−1 BA. Following the transfer of shoots to an elongation medium, the longest shoots (5.4cm) were observed on MS medium supplemented
with 1.0mgl−1 BA + 1.0mgl−1 GA3. The elongated shoots were rooted on MS medium supplemented with different concentrations of indole butyric acid. An assay
of the antioxidant potential of the in vitro-grown tissues revealed that the antioxidant activity of the regenerated shoots
was significantly higher than that of callus and the regenerated plantlets.
KeywordsAntioxidant-6-Benzyladenine-Gibberellic acid-Organogenesis-
Piper nigrum
Trikatu churna is one of the commonly used Ayurvedic formulations
in the traditional system of medicine in India for the treatment of agnimandya,
i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of
Zingiber officinale Roscoe (Zingiberaceae) and fruits of Piper longum L. and
Piper nigrum L. (Piperaceae). The chief objective of the study was to determine
the antianorectic effects of three drugs individually and to compare these effects
with the effect of Trikatu. The activity of the drugs was studied after anorexia
was induced in rats by (1) physical stress arising from immobilization for 60
min; (2) intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS,
100 μg/kg body weight); and (3) intraperitoneal administration of fluoxetine
(8 mg/kg body weight). Similar doses of the extracts were tested on freely
feeding rats and on rats that had been deprived of food for 20 h. Corticotrophinreleasing
factor (CRF, 0.3 μg/rat) can induce anxiogenic-like behavior
and reduced food intake. This model was also studied, and the results were
compared. The components of Trikatu churna failed to individually reverse the
inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-,
fluoxetine- and CRF-induced anorexia. The study provides strong evidence
of the synergistic action of Ayurvedic formulas and also proves the ability of
Trikatu churna to reduce stress and CRF-induced anorexia.
Treatment cost is a major concern for modern medicine in developing countries like India and systematic innovative means to reduce these costs are needed. This article reviews the concept of bioenhancers to reduce treatment costs by increasing drug bioavailability. This concept, based on the Ayurvedic system of medicine, works for a wide range of ingested substances, and has been applied to modern drugs, particularly single chemicals. It offers a fine example of the benefit of integrating an ancient system with modern medicine in both theory and practice.
Rasayana tantra is one of the eight specialties of Ayurveda. It is a specialized practice in the form of rejuvenative recipes, dietary regimen, special health promoting behaviour and drugs. Properly administered Rasayana can bestow the human being with several benefits like longevity, memory, intelligence, freedom from diseases, youthful age, excellence of luster, complexion and voice, optimum strength of physique and sense organs, respectability and brilliance. Various types of plant based Rasayana recipes are mentioned in Ayurveda. Review of the current literature available on Rasayanas indicates that anti-oxidant and immunomodulation are the most studied activities of the Rasayana drugs. Querying in Pubmed database on Rasayanas reveals that single plants as well as poly herbal formulations have been researched on. This article reviews the basics of Rasayana therapy and the published research on different Rasayana drugs for specific health conditions. It also provides the possible directions for future research.
The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t 1/2 beta) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 microg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.
The alcoholic extract of Trikatu churna and its ingredients were evaluated for anthelmintic activity. The dried fruits of Piper nigrum L. (Piperaceae), Piper longum L. (Piperaceae) and rhizome of Zingiber officinale Roscoe. (Zingiberaceae) were powdered and mixed together in equiproportions to get a polyherbal formulation, Trikatu churna. All these three ingredients are spicy, commonly used in our daily diet, also well known for their tremendous therapeutic potential, since from the Vedic period. The alcoholic extract of Trikatu churna and its ingredients were screened for preliminary phytochemical studies and also tested for anthelmintic activity against Pheritima posthuma and recorded the time taken for induction of paralysis and death. Piperazine citrate (10 mg/ml) was included as standard reference and distilled water as control. The results demonstrated that, the extracts of Trikatu churna and its plant ingredients showed the presence of alkaloids, flavonoids, tannins, lignins and steroids, these test samples were also exhibited potent anthelmintic activity, but the highest activity was noticed in Trikatu churna, this might be due to the multifunctional effect of all the three plant ingredients of Trikatu churna. Based on the above results, it is confirmed that, combination of Piper nigrum, Piper longum and Zingiber officinale in Trikatu churna offered promising anthelmintic effect than using the ingredients alone.
Trikatu churna is one of the traditional poly herbal preparation, formed by mixing equal quantities of three important spicy materials such as Piper longum L. (Piperaceae), Piper nigrum L. (Piperaceae) and Zingiber officinale Roscoe (Zingiberaceae). Trikatu is also known as " Three Bitters". The trikatu preparation was reported to contain alkaloids, phenols, tannins, flavanoids, steroids, lignin & saponins. The objective of study is to evaluate the antimicrobial activity of trikatu churna & its individual ingredients with their preliminary phytochemical study. The aqueous extracts of trikatu churna & its each ingredient were tested for antimicrobial activity against certain bacterial strains of Escherichia coli, Staphylococcus aureus by in vitro agar well diffusion method and the results are recorded as the zone of inhibition. Trikatu churna was found to possess higher extent of phytoconstituents with promising antimicrobial activity. INTRODUCTION: Trikatu means three herbs which are having Katu Rasa i.e. a pungent taste. It is the equiproportional mixture of Pimpli (Piper longum L.), Maricha i.e. black pepper (Piper nigrum L.) And Sunthi i.e. dried ginger (Zingiber officinale Roscoe). This combination streamlines the metabolism of the body, this is the reason it is indicated in a wide range of health problems like asthma, fever cold, cough etc. And also used as purgative, carminative, and inobesity, indigestion, high cholesterol, slow metabolism, hypothyroidism, congestion and edema.
When treating children with cancer, long-term venous access is critical. This is especially true in the context of children receiving daily radiation therapy (RT) under general anesthesia. We have previously reported <0.1% risk of complications in complications in over 4,040 pediatric treatments under general anesthesia in our outpatient facility. Here, we present our experience with venous catheter access techniques in children receiving daily proton RT.
After Institutional Review Board approval, we reviewed our center's records between September 9, 2004 and October 23, 2012 with respect to complications and morbidity of indwelling catheters in our pediatric patients.
Vascular access device (VAD) types included: 110 patients with indwelling port-a-cath (PAC), 34 PICC line devices, and 34 central venous catheter (CVC) devices in 170 patients. Median catheter life during RT was 43 days (range 1-86 days) with a total of 7,169 total catheter days while patients received RT. A 14% PAC complication rate included negative blood return (6.3%) and infection (3.6%). Complication rates for PICC and CVC access devices were 38% and 20.5%, respectively (χ(2) P = 0.007 when compared with PAC). Most frequent complications for PICC lines were no blood return (11.7%), and infection or occlusion (8.8% each). CVC complications were breakage (8.8%) and infection (8.8%). Access device replacement rates were 3.6% (PAC), 14.7% (PICC), and 8.8% (CVC).
In the outpatient delivery of RT to children, indwelling ports provide greater convenience, less likelihood of infection or complication, and greater durability than PICC or CVC devices. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
Ethnopharmacological relevance:
Ginger, Zingiber officinale Roscoe, is a common spice and also a widely used medicinal plant in ancient China. Ginger is an ingredient of Ge-Gen-Tang (Kakkon-to; GGT). GGT has been proved to have antiviral activity against human respiratory syncytial virus (HRSV). However, it is unknown whether ginger is effective against HRSV.
Aim of the study:
To find a readily available agent to manage HRSV infection, the authors tested the hypothesis that ginger can effectively decrease HRSV-induced plaque formation in respiratory mucosal cell lines.
Materials and methods:
Effect of hot water extracts of fresh and dried gingers on HRSV was tested by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Ability of ginger to stimulate anti-viral cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA).
Results:
Fresh ginger dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p<0.0001). In contrast, dried ginger didn't show any dose-dependent inhibition. 300 μg/ml fresh ginger could decrease the plaque counts to 19.7% (A549) and 27.0% (HEp-2) of that of the control group. Fresh ginger was more effective when given before viral inoculation (p<0.0001), particularly on A549 cells. 300 μg/ml fresh ginger could decrease the plaque formation to 12.9% when given before viral inoculation. Fresh ginger dose-dependently inhibited viral attachment (p<0.0001) and internalization (p<0.0001). Fresh ginger of high concentration could stimulate mucosal cells to secrete IFN-β that possibly contributed to counteracting viral infection.
Conclusions:
Fresh, but not dried, ginger is effective against HRSV-induced plaque formation on airway epithelium by blocking viral attachment and internalization.
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A review article on Pippali
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