Plant-Derived Natural Compounds for the Treatment of Amyotrophic Lateral Sclerosis: An Update.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease (MND) that typically causes death within 3-5 years after diagnosis. Regardless of the substantial scientific knowledge accrued more than a century ago, truly effective therapeutic strategies remain distant. Various conventional drugs are being used but are having several adverse effects. OBJECTIVE/AIM: The current study aims to thoroughly review plant-derived compounds with welldefined ALS activities and their structure-activity relationships. Moreover, the review also focuses on complex genetics, clinical trials, and the use of natural products that might decrypt the future and novel therapeutics in ALS. METHODS: The collection of data for the compilation of this review work was searched in PubMed Scopus, Google Scholar, and Science Direct. RESULTS: Results showed that phytochemicals like-Ginkgolides, Protopanaxatriol, Genistein, epigallocatechingallate, resveratrol, cassoside, and others possess Amyotrophic lateral sclerosis (ALS) activity by various mechanisms Conclusion: These plant-derived compounds may be considered as supplements for conventional (ALS). Moreover, further preclinical and clinical studies are required to understand the structureactivity relationships, metabolism, absorption, and mechanisms of plant-derived natural agents.

Depression: An Insight into Heterocyclic and Cyclic Hydrocarbon Compounds Inspired from Natural Sources.

Depression, a well-known mental disorder, has global prevalence, affecting nearly 17% of the population. Due to various limitations of the currently available drugs, people have been adopting traditional herbal medicines to alleviate the symptoms of depression. It is notable to mention that natural products, their derivatives, and their analogs are the main sources for new drug candidates of depression. The mechanisms include interplay with γ-aminobutyric acid (GABA) receptors, serotonergic, dopaminergic noradrenergic systems, and elevation of BDNF levels. The focus of this article is to review the role of signalling molecules in depression and highlight the use of plant-derived natural compounds to counter CNS depression.

Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review.

BACKGROUND: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. OBJECTIVE: The present review is focussed to summarize and collect the updated review of information of Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. CONCLUSION: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, antiinflammatory both in vitro and in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.

Possible Pathways of Hepatotoxicity Caused by Chemical Agents.

BACKGROUND: Liver injury induced by drugs has become a primary reason for acute liver disease and therefore posed a potential regulatory and clinical challenge over the past few decades and has gained much attention. It also remains the most common cause of failure of drugs during clinical trials. In 50% of all acute liver failure cases, drug-induced hepatoxicity is the primary factor and 5% of all hospital admissions. METHODS: The various hepatotoxins used to induce hepatotoxicity in experimental animals include paracetamol, CCl4, isoniazid, thioacetamide, erythromycin, diclofenac, alcohol, etc. Among the various models used to induce hepatotoxicity in rats, every hepatotoxin causes toxicity by different mechanisms. RESULTS: The drug-induced hepatotoxicity caused by paracetamol accounts for 39% of the cases and 13% hepatotoxicity is triggered by other hepatotoxic inducing agents. CONCLUSION: Research carried out and the published papers revealed that hepatotoxins such as paracetamol and carbon- tetrachloride are widely used for experimental induction of hepatotoxicity in rats.

Apigenin 7-glucoside from Stachys tibetica Vatke and its anxiolytic effect in rats.

BACKGROUND: Stachys tibetica Vatke (Himalayan or mountain tea) grows abundantly in the tropical and subtropical locations of the world including India, Tibet and China. The traditional healers of Kargil and adjoining areas in Ladakh, Jammu and Kashmir in India use the drug to treat fever, cough, phobias and various mental disorders etc. in the form of a decoction or as a tea. Flavonoids are important components in most herbal teas and play an important role in the management of various brain disorders via mimicking the action of benzodiazepines or through benzodiazepine receptors. AIM OF THE STUDY: The present study aimed to isolate flavonoids from S. tibetica and to evaluate their anxiolytic potential in comparison to reference synthetic (diazepam) and natural (apigenin) molecules. MATERIALS AND METHODS: S. tibetica root powder was extracted with 95% methanol for about 72 h using a soxhlet apparatus and the resultant extract was subjected to isolation procedures, resulting in the isolation of apigenin 7-glucoside and characterisation by various physical and spectrometric analyses. Apigenin 7-glucoside was evaluated for anxiolytic activity in rats in comparison with the reference compounds diazepam and apigenin using the elevated plus maze (EPM) model. RESULTS: Phytochemical investigations of S. tibetica revealed the presence of tannins, phenolics, flavonoids, saponins, glycosides and carbohydrates. A flavonoid glucoside, apigenin 7-glucoside was isolated for the first time from the roots of S. tibetica Vatke. The percentage of time spent and arm entries in the open arms was increased while the arms entries and duration of time spent in closed arms were decreased in the groups treated with apigenin 7-glucoside (which dose). In a similar fashion, diazepam and apigenin also exhibited anxiolytic activity (*p<0.05, **p<0.01). Apigenin 7-glucoside significantly decreased the percentage of head dips in EPM. Apigenin 7-glucoside showed anxiolytic potential comparable to the reference drugs apigenin and diazepam. CONCLUSION: Apigenin 7-glucoside could be an important molecule for the treatment of anxiety and further studies are required to elucidate its possible mechanism of action.

Anti-anxiety activity of Stachys tibetica Vatke.

AIM: S. tibetica Vatke is a herb distributed in the tropical and subtropical regions of the world, including Tibet, China, and India. In India it is found in the cold desert regions of Kargil, Ladakh Valley, and in the mountains of Himachal Pradesh. The traditional practitioners in the Kargil and Ladakh use the natural medicine Stachys tibetica for the treatment of various mental disorders and phobias. The present study is aimed at evaluating the anxiolytic effects of the methanolic extract of the root, stem, leaf, and whole plant material of Stachys tibetica Vatke in rats. METHODS: Powdered materials (1 kg) of each plant part were subjected to extraction in a Soxhlet apparatus with methanol (95%); to yield 12.8%, 8.3%, 17.2%, and 19.6% W/W extractives, respectively. Extracts were evaluated for their anxiolytic effects using the elevated plus maze (EPM) test in rats. RESULTS: In the present study, it was found that the methanolic extracts (200 and 400 mg·kg(-1)) of the root, stem, leaf and whole plant of Stachys tibetica Vatke and diazepam (DZ) increased the time spent and the number of entries in the open arm significantly (**P < 0.01), while they decreased the time spent and the number of entries in the closed arm. At the same time, all of the extracts and DZ decreased the time spent at the center of the maze (latency), along with closed arm returns. The head dip counts increased significantly in the rats treated with DZ, SMR400, SML400 and SMW400 in the open arm of EPM, which was a sign of reduction anxiety. The DZ and SMW did not show the fecal bolus, while other groups had reduced fecal bolus (**P < 0.01) as compared to control. These allied parameters helped to assess the anxiolytic potential of Stachys tibetica Vatke. Whole plant and leaf materials have shown the maximum activity, the root intermediate while the stem had the least anxiolytic activity (*P < 0.05, **P < 0.01) in EPM. CONCLUSION: The results strongly justify the use of this plant for the treatment of anxiety. Further studies are in progress in this laboratory to isolate and identify the components responsible for the anxiolytic activity and the mechanism of action involved.

Animal models of anxiety: a comprehensive review.

Animal models can be used to contribute to understanding the information about molecular mechanisms involved in anxiety and for screening and developing new medications for their treatment that would be impossible in humans. The human studies have established the genetic basis of anxiety and animal studies have been used to attempt to further clarify its genetic determinants. In the field of anxiety research, animal models can be grouped into two main classes. The first involves the animal's conditioned responses to stressful and often painful events (e.g. exposure to electric foot shock) and the second includes ethologically based paradigms and involves the animal's spontaneous or natural reactions (e.g. flight, avoidance and freezing) to stress stimuli that do not explicitly involve pain or discomfort (e.g. exposure to a novel highly illuminated test chamber or to a predator). The current review enlightens the various aspects of animal model of anxiety, which may be used for research purpose.

Coumarins from Angelica archangelica Linn. and their effects on anxiety-like behavior.

UNLABELLED: TRADITIONAL RELEVANCE: Angelica archangelica Linn. (Apiaceae) is an herb distributed in tropical and subtropical regions of the world. Both in Chinese and Indian system of medicine, it is used for nervous disorders including anxiety, anorexia, migraine and other cerebral diseases. AIM OF STUDY: To evaluate the anxiolytic potential of non polar coumarins isolated from A. archangelica Linn. METHODS AND RESULTS: A. archangelica Linn. (1 kg) was subjected to extraction in a soxhlet apparatus with petroleum ether (40-60 °C), yield 6.9% w/w. The extract of petroleum ether produced a yellow colored precipitate (YP) which was evaluated for anxiolytic like effect using EPM test and was found significant (**P<0.01) in doses of 5 and 10 mg/kg, po. The precipitate was shown to be a mixture of seven constituents in HPTLC and six on the TLC plate which were further subjected to separation by preparative TLC. Non polar coumarins were isolated namely imperatorin (IM) and isoimperatorin (IIM). YP, IM, IIM were tested for anxiolytic like effects in a dose of 5mg/kg, po along with DZ (1mg/kg, po) using EPM, Light & dark arena and hole board models in rats. All the test drugs were found to have significant (*P<0.05, **P<0.01) activity. IM and IIM have the potential to reduce anxiety but yellow precipitate showed the most promising activity as compared to isolated coumarins. This effect may be due to the synergistic action of all compounds present in the YP or by multiple mechanism of action. The test drugs may have the potential for different receptors. CONCLUSION: The mixture of coumarins isolated from A. archangelica and its constituents imperatorin and isoimperatorin have the potential to reduce anxiety but it is the mixture which have more significant activity as compared to its individual components.

The genus Crataegus: chemical and pharmacological perspectives

Traditional drugs have become a subject of world importance, with both medicinal and economical implications. A regular and widespread use of herbs throughout the world has increased serious concerns over their quality, safety and efficacy. Thus, a proper scientific evidence or assessment has become the criteria for acceptance of traditional health claims. Plants of the genus Crataegus, Rosaceae, are widely distributed and have long been used in folk medicine for the treatment of various ailments such as heart (cardiovascular disorders), central nervous system, immune system, eyes, reproductive system, liver, kidney etc. It also exhibits wide range of cytotoxic, gastroprotective, anti-inflammatory, anti-HIV and antimicrobial activities. Phytochemicals like oligomeric procyanidins, flavonoids, triterpenes, polysaccharides, catecholamines have been identified in the genus and many of these have been evaluated for biological activities. This review presents comprehensive information on the chemistry and pharmacology of the genus together with the traditional uses of many of its plants. In addition, this review discusses the clinical trials and regulatory status of various Crataegus plants along with the scope for future research in this aspect.

Anti-anxiety activity of successive extracts of Angelica archangelica Linn. on the elevated T-maze and forced swimming tests in rats.

OBJECTIVE: Angelica archangelica Linn. is widely used in food and liquor preparations and also in Kashmiri folk medicine to reduce anxiety. We evaluated the anxiolytic effect of successive extracts of A. archangelica linn. (SAE) on rats tested in the elevated T-maze test (an animal model of generalized anxiety) at doses that exhibit antidepressant-like activity in humans. METHODS: A. archangelica (1 kg) was subjected to successive extraction in a soxhlet apparatus with solvents [petroleum ether (40-60 degrees C), chloroform, ethyl acetate, methanol and decoction with water] in order of increasing polarity (yield: 6.9%, 7.3%, 5.1%, 11.88% and 8.2% w/w, respectively). SAE were evaluated for anxiolytic effects using the elevated T-maze and forced swimming tests in rats. RESULTS: Oral dosing of diazepam (1 mg/kg) and extracts (50, 100 and 200 mg/kg) clearly showed an anxiolytic-like profile in the elevated T-maze test: it increased one-way escape and decreased inhibitory avoidance on the first, third and seventh day. In the forced swimming test, imipramine and SAE showed antidepressant- and anxiolytic-like effects as reflected by increased climbing time, swimming time and decreased immobility time on the first, third and seventh day. Aqueous and methanol extracts showed the most, petroleum ether (40-60 degrees C) and chloroform intermediate, and ethyl acetate the least anxiolytic activity (*P<0.05, **P<0.01, ***P< 0.001) in both models. CONCLUSIONS: These results suggest the anti-anxiety activity of various extracts of A. archangelica and strongly justify its use in traditional Indian medicine for the treatment of anxiety.

Evaluation of anti-inflammatory potential of leaf extracts of Skimmia anquetilia.

OBJECTIVE: To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. METHODS: Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1% w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmia anquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method. RESULTS: The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40% and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. CONCLUSIONS: The present investigation has confirmed the anti-inflammatory activity of Skimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti- inflammatory agent.

Anti-anxiety Activity of Methanolic Extracts of Different Parts of Angelica archangelica Linn.

Angelica archangelica Linn.is a herb distributed in tropical and subtropical regions of the world. In Indian and Chinese system of medicine, it is used for nervous disorders and cerebral diseases. Previously the aqueous extract of the A. archangelica was evaluated for anxiolytic activity and was found to have significant potential for the same. The present study is aimed to evaluate the anxiolytic activity of methanol extract of root (MER), stem (MES), leaf (MEL), fruit (MEF) and whole plant (MEW) of Angelica archangelica Linn. All the extracts (MER, MES, MEL, MEF and MEW) were evaluated for anxiolytic effects using elevated plus maze test (EPM) model in rats. Methanol extracts of different parts of A.archangelica had increased number of entries and time spent in open arms while they decreased the number of entries and duration of time spent in closed arm of the EPM. In a similar fashion, the diazepam increased the percentage of time spent and percentage of arm entries in the open arms (*P <0.05, **P <0.01). Whole plant and the root had the maximum, leaf and fruits showed intermediate, while stem had the least anxiolytic activity (*P <0.05, **P <0.01) in EPM (Figure 1-5). The head dip count in DZ, SMR400, SML400, SMF400 and SMW400 in open arm are significantly shown in Table 1. The DZ, SMF400 and SMW did not show the fecal bolus while other groups were reduced the fecal bolus significantly (**P <0.01) as compared to control (Table 1). Whole plant and leaf showed the most, root and fruit the intermediate and stem the least anxiolytic activity (**P <0.01) in EPM.

A review of immunomodulators in the Indian traditional health care system.

Some of the medicinal plants valued in Ayurvedic Rasayana for their therapeutic potential have been scientifically investigated with promising results. A number of plant-based principles have been isolated with potential immunomodulatory activity that can explain and justify their use in traditional medicine in the past and can form the basis for further research in the future as well. The aim of this review is to highlight results of research done on immunomodulators of plant origin. The selection of papers was made using the most relevant databases for the biomedical sciences on the basis of their ethnopharmacological use. Many plants and some phytoconstituents responsible for immunomodulation have been explained. The review also discusses biological screening methods for various plant drugs that focus on revealing the mechanism involved in immunomodulation. This work shall hopefully encourage researchers to undertake further work on medicinal plants with potential immunomodulatory activity.