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Abstract
<p class="first" id="d4681816e132">Cerebral ischemia reperfusion injury (CIRI), one
of the major causes of death from
stroke in the world, not only causes tremendous damage to human health, but also brings
heavy economic burden to society. Current available treatments for CIRI, including
mechanical therapies and drug therapies, are often accompanied by significant side-effects.
Therefore, it is necessary to discovery new strategies for treating CIRI. Many studies
have confirmed that the herbal medicine has the advantages of abundant resources,
good curative effect and little side effects, which can be used as potential drug
for treatment of CIRI through multiple targets. It's known that oral administration
commonly has low bioavailability, and injection administration is inconvenient and
unsafe. Many drugs can't delivery to brain through routine pathways due to the blood-brain-barrier
(BBB). Interestingly, increasing evidences have suggested the nasal administration
is a potential direct route to transport drug into brain avoiding the BBB and has
the characteristics of high bioavailability for treating brain diseases. Therefore,
intranasal administration can be treated as an alternative way to treat brain diseases.
In the present review, effective methods to treat CIRI by using active ingredients
derived from herbal medicine through nose to brain drug delivery (NBDD) are updated
and discussed, and some related pharmacological mechanisms have also been emphasized.
Our present study would be beneficial for the further drug development of natural
agents from herbal medicines via NBDD.
</p>
This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012. In the case of all approved therapeutic agents, the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide. As mentioned in the 2012 review, we have continued to utilize our secondary subdivision of a "natural product mimic", or "NM", to join the original primary divisions and the designation "natural product botanical", or "NB", to cover those botanical "defined mixtures" now recognized as drug entities by the U.S. FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over the time frame from around the 1940s to the end of 2014, of the 175 small molecules approved, 131, or 75%, are other than "S" (synthetic), with 85, or 49%, actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the anti-infective area being dependent on natural products and their structures. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore it is considered that this area of natural product research should be expanded significantly.
In the United States stroke is the third leading cause of death and the leading cause of disability. Brain injury following stroke results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation and apoptosis. There are very few treatments for stroke and the development of new treatments requires a comprehensive understanding of the diverse mechanisms of ischemic brain damage that are responsible for neuronal death. Here, we discuss the underlying pathophysiology of this devastating disease and reveal the intertwined pathways that are the target of therapeutic intervention.
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