A Possible Synergistic Herbal Solution for COVID-19.

The COVID-19 pandemic has provided an opportunity for repurposing of drugs, including complex, natural drugs, to meet the global need for safe and effective antiviral medicines which do not promote multidrug resistance nor inflate medical costs. The author herein describes his own repurposing of herbal tinctures, previously prepared for oncology, into a possibly synergistic, anti-COVID 41 "herb" formula of extracts derived from 36 different plants and medicinal mushrooms. A method of multi-sample in vitro testing in green monkey kidney vero cells is proposed for testing the Hypothesis that even in such a large combination, antiviral potency may be preserved, along with therapeutic synergy, smoothness, and complexity. The possibility that the formula's potency may improve with age is considered, along with a suitable method for testing it. Collaborative research inquiries are welcome.

A review of pears (Pyrus spp.), ancient functional food for modern times.

BACKGROUND: Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia. METHODS: We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears. RESULTS: We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro, in vivo, and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, -hyperlipidemic, -inflammatory, -mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM2.5 among high susceptible people with multiple underlying diseases. CONCLUSION: For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.

High environmental stress yields greater tocotrienol content while changing vitamin e profiles of wild emmer wheat seeds.

Vitamin E is an essential human nutrient that was first isolated from wheat. Emmer wheat, the cereal of Old World agriculture and a precursor to durum wheat, grows wild in the Fertile Crescent. Evolution Canyon, Israel, provides a microsite that models effects of contrasting environments. The north-facing and south-facing slopes exhibit low and high stress environments, respectively. Wild emmer wheat seeds were collected from both slopes and seed tocochromanol contents measured to test the hypothesis that high stress alters emmer wheat seed tocol-omics. Seeds from high stress areas contained more total vitamin E (108±15 nmol/g) than seeds from low stress environments (80±17 nmol/g, P=.0004). Vitamin E profiles within samples from these different environments revealed significant differences in isoform concentrations. Within each region, ß- plus γ-tocotrienols represented the highest concentration of wheat tocotrienols (high stress, P<.0001; low stress, P<.0001), while α-tocopherol represented the highest concentration of the tocopherols (high stress, P=.0002; low stress, P<.0001). Percentages of both δ-tocotrienol and δ-tocopherol increased in high stress conditions. Changes under higher stress apparently are due to increased pathway flux toward more tocotrienol production. The production of more δ-isoforms suggests increased flow through a divergent path controlled by the VTE1 gene. Hence, stress conditions alter plant responses such that vitamin E profiles are changed, likely an attempt to provide additional antioxidant activity to promote seed viability and longevity.

Anticancer potential of aloes: antioxidant, antiproliferative, and immunostimulatory attributes.

Aloe is a genus of medicinal plants with a notable history of medical use. Basic research over the past couple of decades has begun to reveal the extent of Aloe's pharmaceutical potential, particularly against neoplastic disease. This review looks at Aloe, both the genus and the folk medicine, often being called informally "aloes", and delineates their chemistry and anticancer pharmacognosy. Structures of key compounds are provided, and their pharmacological activities reviewed. Particular attention is given to their free radical scavenging, antiproliferative, and immunostimulatory properties. This review highlights major research directions on aloes, reflecting the enormous potential of natural sources, and of the genus Aloe in particular, in preventing and treating cancer.

Anticancer attributes of desert plants: a review.

The ever-increasing emergence of the resistance of mammalian tumor cells to chemotherapy and its severe side effects reduces the clinical efficacy of a large variety of anticancer agents that are currently in use. Thus, despite the significant progress in cancer therapeutics in the last decades, the need to discover and to develop new, alternative, or synergistic anticancer agents remains. Cancer prevention or chemotherapy based on bioactive fractions or pure components derived from desert plants with known cancer-inhibiting properties suggests promising alternatives to current cancer therapy. Plants growing on low nutrient soils and/or under harsh climatic conditions, such as extreme temperatures, intense solar radiation, and water scarcity, are particularly susceptible to attack from reactive oxygen species and have evolved efficient antioxidation defense systems. The many examples of desert plants displaying anticancer effects as presented here indicates that the same defensive secondary metabolites protecting them against the harsh environment may also play a protective or a curative role against cancer, as they also do against diabetes, neurodegenerative, and other acute and chronic diseases. The present review highlights a plethora of studies focused on the antineoplastic properties of desert plants and their prinicipal phytochemicals, such as saponins, flavonoids, tannins, and terpenes. Although many desert plants have been investigated for their antitumor properties, there are many that still remain to be explored - a challenge for the prospective cancer therapy of the future.

'Tocol-omic' diversity in wild barley, short communication.

Hordeum spontaneum, wild barley, is the direct progenitor of domestic barley, Hordeum vulgare, an economically important ingredient of animal feed, beer, soy sauce, and more recently, of nutraceuticals. Domestic barley has also been used in the past as a medicine. Barley is a rich source of tocotrienols, with α-tocotrienol being the most prevalent. Wild barley seeds were harvested from ecogeographically diverse areas across the Fertile Crescent, and the tocopherol (α-δ) and tocotrienol (α-δ) contents were determined. Diversity differences in individual and total 'tocol' values were significant between and within specific countries, and were significantly correlated with temperature. Wild barley may be used in the future to improve functional qualities of domestic barley. 'Tocolome' and 'tocolomics' are proposed to encompass all tocols and potentially synergy-enhancing 'entourage' compounds that may occur in tocols' 'metabolomic neighborhoods', aiding the standardized manufacture of complex barley derivatives for nutraceutical and pharmaceutical functions.

Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms.

Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease.

Pomegranate (Punica granatum) seed linolenic acid isomers: concentration-dependent modulation of estrogen receptor activity.

Pomegranate (Punica granatum) seed linolenic acid isomers were evaluated as selective estrogen receptor modulators (SERMs) in vitro. Punicic acid (PA) inhibited (IC(50)) estrogen receptor (ER) alpha at 7.2 microM, ERbeta at 8.8 microM; alpha-eleostearic acid (AEA) inhibited ERalpha/ERbeta at 6.5/7.8 microM. PA (not AEA) agonized ERalpha/ERbeta (EC(50)) at 1.8/2 microM, antagonizing at 101/80 microM. AEA antagonized ERalpha/ERbeta at 150/140 microM. PA and AEA induced ERalpha and ERbeta mRNA expression in MCF-7, but not in MDA-MB-231. Overall, the results show PA and AEA are SERMs.

Pomegranate fruit extract impairs invasion and motility in human breast cancer.

PURPOSE: Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity. EXPERIMENTAL DESIGN: The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines. The effects of the PFE on NF-kB-regulated cellular processes such as cell survival, proliferation, and invasion were also examined. RESULTS: Analytical characterization of the bioactive components of the PFE revealed active constituents, mainly ellagitannins and phenolic acids in the aqueous PFE and conjugated octadecatrienoic acids in the lipid PFE derived from seeds.The aqueous PFE dose-dependently inhibited NF-kB-dependent reporter gene expression associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression. CONCLUSION: Inhibition of motility and invasion by PFEs, coincident with suppressed RhoC and RhoA protein expression, suggests a role for these defined extracts in lowering the metastatic potential of aggressive breast cancer species.

Ficus spp. (fig): ethnobotany and potential as anticancer and anti-inflammatory agents.

This review explores medieval, ancient and modern sources for ethnopharmacological uses of Ficus (fig) species, specifically for employment against malignant disease and inflammation. The close connection between inflammatory/infectious and cancerous diseases is apparent both from the medieval/ancient merging of these concepts and the modern pharmacological recognition of the initiating and promoting importance of inflammation for cancer growth. Also considered are chemical groups and compounds underlying the anticancer and anti-inflammatory actions, the relationship of fig wasps and fig botany, extraction and storage of fig latex, and traditional methods of preparing fig medicaments including fig lye, fig wine and medicinal poultices.

Punica granatum: heuristic treatment for diabetes mellitus.

The current diabetes epidemic is a global concern with readily available effective therapies or preventative measures in demand. One natural product with such potential is the pomegranate (Punica granatum), with hypoglycemic activity noted from its flowers, seeds, and juice in canons of the traditional folk medicines of India. The mechanisms for such effects are largely unknown, though recent research suggests pomegranate flowers and juice may prevent diabetic sequelae via peroxisome proliferator-activated receptor-gamma binding and nitric oxide production. Pomegranate compounds associated with antidiabetic effects include oleanolic, ursolic, and gallic acids. Pomegranate fractions and their active compounds hold potential and are worthy of further investigations as safe and effective medical treatments for diabetes mellitus and its pathological consequences.

Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer.

The last 7 years have seen over seven times as many publications indexed by Medline dealing with pomegranate and Punica granatum than in all the years preceding them. Because of this, and the virtual explosion of interest in pomegranate as a medicinal and nutritional product that has followed, this review is accordingly launched. The pomegranate tree, Punica granatum, especially its fruit, possesses a vast ethnomedical history and represents a phytochemical reservoir of heuristic medicinal value. The tree/fruit can be divided into several anatomical compartments: (1) seed, (2) juice, (3) peel, (4) leaf, (5) flower, (6) bark, and (7) roots, each of which has interesting pharmacologic activity. Juice and peels, for example, possess potent antioxidant properties, while juice, peel and oil are all weakly estrogenic and heuristically of interest for the treatment of menopausal symptoms and sequellae. The use of juice, peel and oil have also been shown to possess anticancer activities, including interference with tumor cell proliferation, cell cycle, invasion and angiogenesis. These may be associated with plant based anti-inflammatory effects, The phytochemistry and pharmacological actions of all Punica granatum components suggest a wide range of clinical applications for the treatment and prevention of cancer, as well as other diseases where chronic inflammation is believed to play an essential etiologic role.

Transcendental meditation: a double-edged sword in epilepsy?

Transcendental Meditation (TM) is derived from ancient yogic teachings. Both short- and long-term physiological correlates of TM practice have been studied. EEG effects include increased alpha, theta, and gamma frequencies and increased coherence and synchrony. Neuronal hypersynchrony is also a cardinal feature of epilepsy, and subjective psychic symptoms, apnea, and myoclonic jerking are characteristic of both epileptic seizures and meditative states. Clinical vignettes have highlighted the potential risk of human kindling from repetitive meditation in persons practicing TM, but clinical studies of similar techniques suggest that meditation may also be a potential antiepileptic therapy. Future clinical studies of meditating subjects using video/EEG monitoring are warranted to determine whether behavioral phenomena have an underlying epileptic basis, and prospective clinical trials of TM in subjects with well-delineated epilepsy syndromes are necessary to establish the safety of this technique and its potential efficacy for seizure reduction and improvement of quality of life.

Beware of pomegranates bearing 40% ellagic Acid.

A recent profusion of pomegranate nutraceutical products, "standardized to 40% ellagic acid," has appeared in the marketplace. This Perspective reviews the chemical and functional studies of pomegranate as well as the virtues and dangers of ellagic acid, and concludes that synergy among the various pomegranate fractions and phytochemicals is the most important factor for assessing strength of pomegranate nutraceutical preparations, and not simply the concentration of ellagic acid. Ellagic acid concentration in final products is likely to have an optimal therapeutic range, which very likely is less than 40%. The wisdom of designing and engineering pomegranate nutraceutical products to maximize therapeutic or chemopreventive synergy is suggested, as opposed to preparations that are designed and engineered simply to maximize the concentration of a single phytochemical. The implications of this strategy may be generalized for the optimization of nutraceutical preparations from other medicinal plants as well.

Meditation and epilepsy: a still hung jury.

Meditation has been advocated as a treatment for several medical problems, including epilepsy. Conversely, concern has been raised that meditation may aggravate or even precipitate epilepsy. We present a case of new onset mesial temporal lobe epilepsy in a young woman meditator lacking other apparent risk factors for epilepsy as a springboard for a balanced discussion concerning the potential relationship between meditation and epilepsy, and a criticism of the current literature in this field. Prospective clinical studies of meditators with video-electroencephalography and clinical trials of meditation in refractory epilepsy patients are needed to resolve current controversies concerning meditation and epilepsy.

Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells.

Pomegranate (Punica granatum) is an ancient fruit with exceptionally rich ethnomedical applications. The peel (pericarp) is well regarded for its astringent properties; the seeds for conferring invulnerability in combat and stimulating beauty and fertility. Here, aqueous fractions prepared from the fruit's peel and fermented juice and lipophilic fractions prepared from pomegranate seeds were examined for effects on human epidermal keratinocyte and human dermal fibroblast function. Pomegranate seed oil, but not aqueous extracts of fermented juice, peel or seed cake, was shown to stimulate keratinocyte proliferation in monolayer culture. In parallel, a mild thickening of the epidermis (without the loss of ordered differentiation) was observed in skin organ culture. The same pomegranate seed oil that stimulated keratinocyte proliferation was without effect on fibroblast function. In contrast, pomegranate peel extract (and to a lesser extent, both the fermented juice and seed cake extracts) stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 (MMP-1; interstitial collagenase) production by dermal fibroblasts, but had no growth-supporting effect on keratinocytes. These results suggest heuristic potential of pomegranate fractions for facilitating skin repair in a polar manner, namely aqueous extracts (especially of pomegranate peel) promoting regeneration of dermis, and pomegranate seed oil promoting regeneration of epidermis.

Pomegranate (Punica granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across Matrigel.

Four pure chemicals, ellagic acid (E), caffeic acid (C), luteolin (L) and punicic acid (P), all important components of the aqueous compartments or oily compartment of pomegranate fruit (Punica granatum), and each belonging to different representative chemical classes and showing known anticancer activities, were tested as potential inhibitors of in vitro invasion of human PC-3 prostate cancer cells in an assay employing Matrigel artificial membranes. All compounds significantly inhibited invasion when employed individually. When C, P, and L were equally combined at the same gross dosage (4 microg/ml) as when the compounds were tested individually, a supradditive inhibition of invasion was observed, measured by the Kruskal-Wallis non-parametric test.

Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions.

We investigated whether dissimilar biochemical fractions originating in anatomically discrete sections of the pomegranate (Punica granatum) fruit might act synergistically against proliferation, metastatic potential, and phosholipase A2 (PLA2) expression of human prostate cancer cells in vitro . Proliferation of DU 145 human prostate cancer cells was measured following treatment with a range of therapeutically active doses of fermented pomegranate juice polyphenols (W) and sub-therapeutic doses of either pomegranate pericarp (peel) polyphenols (P) or pomegranate seed oil (Oil). Invasion across Matrigel by PC-3 human prostate cancer cells was measured following treatment with combinations of W, P and Oil such that the total gross weight of pomegranate extract was held constant. Expression of PLA2, associated with invasive potential, was measured in the PC-3 cells after treatment with the same dosage combinations as per invasion. Supra-additive, complementary and synergistic effects were proven in all models by the Kruskal-Wallis non-parametric H test at p < 0.001 for the proliferation tests, p < 0.01 for invasion, and p < 0.05 for PLA2 expression. Proliferation effects were additionally evaluated with CompuSyn software median effect analysis and showed a concentration index CI < 1, confirming synergy. The results suggest vertical as well as the usual horizontal strategies for discovering pharmacological actives in plants.

Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells.

We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO(2)-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED(50)) was 70 microg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED(50) = 250 g/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G(2)/M cells (P <.05) by treatment with Oil (35 microg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 microg/mL) resulted in significant 2.3 +/- 0.001-fold (mean +/- SEM) up-regulation of the cyclin-dependent kinase inhibitor p21((waf1/cip1)) (P <.01) and 0.6 +/- 0.14-fold down-regulation of c-myc (P <.05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.