HIGH FLAVONOID HERBS AND VASCULAR HEALTH (with a focus on Hibiscus)

By Dr Jillian Stansbury (italicized & bolded text by CJK for emphasis)

High flavonol plants have been discussed in the herbal literature for several decades now, with an emphasis on
broad anti oxidant and antiinflammatory activity combined with virtually no toxicity and an overall nutritive
quality. The research on antioxidant and inflammatory activity will not be presented here as these activities have
been well reported and reported on for some time now. Rather, this paper will briefly review the lesser well known
hormonal activities of flavonoids, and then focus on new research emerging on the cardiovascular and other effects
of flavonoids in Hibiscus species.
Flavonoid Aromatase Inhibitors
Numerous flavonoid molecules have been shown to be aromatase inhibitors. Grape seeds and grape juice, red wine,
blueberries, pomegranates, and numerous brightly pigmented plants high in flavonoids are potent
antioxidants and antiinflammatories as well as noted to improve hormonal balance via a
variety of mechanisms. The less brightly pigmented Isoflavones, prominent in the legume family are also
among the widely studied aromatase inhibitors. These are probably best in prevention of hormonal cancers, but
may also be attempted aggressively with dietary and herbal supplemental measures in cases or prostatic carcinoma.
Numerous flavonoids have had extensive research as to their hormonal activity. In one study nearly 30 randomly
selected flavonoids, both natural and synthetic were tested for aromatase activity. Over half displayed aromatase
inhibition with the natural compounds apigenin, hesperitin and chrysin being the most powerful.1 Chrysin,
quercitin, kameferol and red wine pigments2 are among the earliest researched flavonoids reported to have
vascular and hormonal effects, including aromatase inhibition. Among the many positive physiologic effects of
the flavonoids in red wine is aromatase inhibition.3 Chrysin is also found in honey and propolis4 and noted to be
an aromatase inhibitor. Flavonoids in Grape seed (Vitis vinifera) procyanidin flavonoids inhibit aromatase
enzymes.5 Vitis vinifera (wine grape) flavonoids in an aqueous vehicle have been demonstrated to improve
perfusion in cases of bladder obstruction lending credence to the idea that ischemia contributes to symptoms in
med with BPH.6 Althea rosea (Hollyhock) flavonoids are noted to affect aromatase activity in testicular cells, as
well as antagonize estrogen beta receptors, rather than alpha.7 Punica granatum, Pomegranate juice is a rich
source of powerfully antioxidant polyphenol flavonoids is noted to act as an aromatase inhibitor and deter growth
in breast cancer cell lines.8 Catechins, particularly well researched in Green Tea, Camellia sinensis is reported to
be an aromatase inhibitor.9 Green tea catechins have also been shown to be directly inhibitory to prostate cancer
cell lines.10
Hibicsus species and Flavonoid Activities
Hibiscus is a large genus in the Malvacea family and includes several hundred species all native to warm
temperate, or especially tropical and subtropical climes. Because of their beauty, Hibiscus is planted ornamentally
around the world, and the beautiful shrubs also attract bees, butterflies, and hummingbirds to the garden.
Lepidoptora family moths particularly are attracted to Hibiscus flowers which serve as a important food source for
larvae.
In India, Hibiscus flowers are among those sacred flowers and objects offered by Hindus to the Goddess kali and
Lord Ganesh. In Tahiti, the wearing of a red Hibiscus flower behind the ear by a woman is an indication that she is
seeking a spouse and available for marriage.
The word Hibiscus is said to have originated with Pedanius Dioscorides having used the word around 50 AD to
refer to a related plant presently known as Althea officinalis. Hibiscus cannabinus, so named because of its hemp
like leaves, goes by the common name Kenaf is used for fiber and paper making. Hibiscus sabdariffa is native to
Africa but now well established in many tropical regions around the world. Hibiscus sabdariffa has been the
subject of numerous studies discussed in this paper and goes by the common name Roselle. Roselle is also
harvested as a vegetable and used to prepare jams and drinks, particularly in the Caribbean. One such drink,
known as "Sorrel" is prepared with the sour hibiscus flower tea combined with other herbs and spices and often
sweetened with sugar and spiked with rum or wine as a holiday punch. Hibiscus flower teas have also been
referred to as "rose" teas even though they are not in the rose family. One commercial topical product is being
marketed under the name of Roselle due to the history of this common name. Hibiscus flower teas are enjoyed
around the world, referred to as Flor de Jamaica in Mexico, Gongura in India, Bissap in West Africa, and Karkade
is Egypt. Hibiscus rosa sinensis are also believed to have medicinal properties and widely used in herbal teas,
simply as a refreshing beverage, to treat coughs, and to provide cooling astringent effects in hot and damp
conditions. In temperate zones, the above Hibiscus species do not thrive, but the related Hibiscus syriacus, going
by the common names Rose of Althea or Rose of Sharon are attractive ornamental shrubs, but the flowers do not
import the same flavor, color, nor likely medicinal effects as the tropical species. Hibiscus syriacus is the national
flower of South Korea and Hibiscus rosa sinensis is native to Asia and is the national flower of Malaysia and the
state flower of Hawaii. Hibiscus tiliaceas or Sea Hibiscus is native to Oceania and introduced into Australia in the
early 1800s.
In India, Hibiscus flowers are sometimes decocted in oil, which is then used on the hair to prevent hair loss
and graying. The leaves are also ground into a powder and made into a paste with water and also been used on the
hair and scalp as a conditioner. There are many other species of Hibiscus, some native to Hawaii, and Hibiscus
enthusiasts work to create multi colored varieties of Hibiscus flowers by controlling pollination. Many Hibiscus
flowers have also been used around the world as dye plants. Cotton, Okra and Hollyhocks are all relatives of
Hibiscus and members of the Malvacea family.
General Research on Hibiscus
Many research reports on the medicinal uses of Hibiscus use the term "calyces" which simply means the flower
petals. Anthocyanins are the main flavonoid group in Hibiscus sabdariffa and include delphinin (also found in the
Ranunulacea Delphinium ), sambubiosides (also in the Caprifoliacea Sambucus), and cyanidin. In addition to the
flavonoids, other phenolic compounds include hydroxycitric and chlorogenic acids. Hibiscus syriacus has been
found to contain a sequiterpene named Hydoroxyhiscone that has an anti aging effect on neutrophils in a manner
stabilizing the prolonging the life of elastase elaboration by the blood cell.11
Hibiscus sabdariffa is one of the most commonly used species of Hibiscus. In Mexico, the common knowledge
regarding Flor de Jamaica is that it has benefits for the kidneys and is a natural diuretic and antiparasitic agent.
The main species of Hibiscus in Mexico is H. sabdariffa and was believed to have been introduced in the colonial
period. More recently Hibiscus drinks and teas have gained popularity as a cholesterol lowering agent and to
support weight loss. A recent (2010) review of research on Hibiscus sabdariffa reported 4 human clinical trials to
date but reported that the studies were for short duration and of poor quality and that larger studies were needed.12
In Mexico, Hibiscus flower tea is widely used as a diuretic and cooling "refresco" beverage, for treating GI
disorders, liver diseases, fevers and heat in the body, and for high cholesterol and hypertension.
Hibiscus esculentus or Okra is a commonly consumed vegetable, particularly in Africa. Quercitin and other
isoflavonoids have been identified in Okra and potent antioxidant activities have also been confirmed. Eating
foods high in antioxidants over a lifetime, are believed to be association with a lower risk of cancer and many
chronic inflammatory diseases.13
Hibiscus Flavonoids are Antiinflammatory (Of course!)
inclusion in skin
Hibiscus sabdariffa has displayed antioxidant effects and researchers have reported its
formulae helps to improve the absorption and penetration of other ingredients.14 This same
species has been used folklorically in China for hypertension and a variety of inflammatory conditions. In addition
to flavonoids, Hibiscus sabdariffa also contains phenolic acids credited with medicinal effects as well. The
aqueous extract (tea) of Hibiscus flowers has been shown to protect monocytes from inflammatory damages and to
modulate the release of inflammatory cytokines.15 A flavonoid in Hibiscus abelmoschus seeds has been reported
to protect dermal epithelium by acting like heparin sulfate in directing the release of dermal growth factors and
stimulated the synthesis of sulphated glycosaminoglycans. 16
Hibiscus Flavonoids Reduce Liver Inflammation
Hibiscus sabdariffa has antioxidant properties17 and contains anthocyanins have been shown to induce phase II
drugs detoxification enzymes.18 Other researchers have also reported hepatoprotective effects in fish from Hibiscus.
One recently published study (Jan 2011) reports that Hibiscus sabdariffa protects liver cells from the damaging
effects of carbon tetrachloride. [Jillian commented in talk that the particularly toxic chemical is used in dry
cleaning. It is usually very difficult to protect the liver from this very toxic chemical that hibiscus helps to detoxify.
Therefore it is reasonable to surmise that hibiscus also would also protect from lesser liver toxins & challenges]
Researchers measured LDH, and SGOT, and SGPT and other markers of liver inflammation and reported that
Hibiscus was particularly helpful when used prior to exposure to hepatotoxins serving to prevent inflammatory and
oxidative damage to liver cells.19 Hibiscus sabdariffa has been shown to prevent liver injury in animals exposed to
hepatoxins by mechanisms believed to be involved with reducing oxidative stress in the liver as evidenced by
lower inflammatory markers in treated animals compared to controls.20
Hibiscus Flavonoids Support Renal Excretion and Function
Hibiscus sabdariffa has been shown to decrease oxalates in
the serum and promote urinary excretion
of oxalate suggesting possible utility in cases of gout and urinary inflammation and stones.
Histological investigations report that Hibiscus can decrease the amount of calcium oxalate deposited in renal cells
and tissues.21 Hibiscus sabdariffa has also been shown to reduce oxidative stress in the kidneys, particularly in
animal test models of diabetes and diabetic nephropathy. H sabdariffa aqueous extracts have been shown to
reduce lipid peroxidation, increase catalase and gluathione anti inflammatory activity, and decrease plasma lipids,
typically elevated in the diabetic state. Furthermore, Hibiscus extracts are able to improve hyperglycemia induce
osmotic diuresis due to effects in the renal proximal tubules (a hydropic change).22 One human clinical trial
followed patients with Metabolic Syndrome and evaluate the effects of H. sabdariffa powder on serum lipid
profiles. A daily dose of 100 mg of H. sabdariffa was administered in capsules for one month to one group of
randomly selected test subjects and compared to controls receiving a placebo. After one month the group
receiving the Hibiscus capsules displayed significantly lower lipids, glucose and insulin resistance compared to
controls.23
Hibiscus Flavonoids May Offer Chemo-protection
One group of researchers credited Hibiscus with chemoprotective properties owing to the antioxidant effect of the
anthocyanins and phenolic compounds.24 Inhibition of LDL oxidation, oxidative damage to hepatocytes, and
support of smooth muscle cell development are among the specific chemoprotective effects reported. Furthermore,
the same researchers reported Hibiscus flower extracts to promote apoptosis in cancer cells and leukemia cell lines
and protect the kidneys from inflammatory damage in diabetic research models. Antimutagenic effect have been
reported from Hibiscus rosa sinensis flowers. 25 H. rosa sinensis was shown to protect animals from nitrites and
Salmonella toxins but to be less potent than lotus flowers, and Curcuma and Guayaba flowers. The researchers
proposed that the flavonoids found in flowers were responsible for the anitmutagenic effects.

Hibiscus Species have CNS and Neuro-protective Effects

Hibiscus rosa sinensis has been shown to prevent the neurological symptoms induced by reserpine toxicity, thus
suggesting central nervous system effects. Hibiscus asper is another species of Hibsicus found mainly in Africa
and India where the roots are sometimes prepared as a vegetable, the stems and stalks as a fiber, and the leaves as
a medicine for inflammation and depression.
Recently published animal studies show that Hibiscus asper species may have an anxiolytic effect due to CNS
effects involving dopaminergic pathways,26 explaining the folkloric use for depression. Another species of
Hibiscus, H. cannabinus, sometimes going by the common name Kenaf, has been shown to inhibit tyrosinase, an
enzyme involved in the synthesis of monoamines.27 Kenaf seeds are high in essential fatty acids, phytosterols, and
vitamin E, the sum of which many credit to providing anti inflammatory activity. One group of researchers
demonstrated that Kenaf seed extracts could halt the progression of early colon cancer in rat models.28 Other
researchers have repeated these findings confirming a neuroprotective effect of Hibiscus rosa sinensis.29 A
common animal research model is to induce states of cerebral hypoxia and test for agents capable of preventing
ischemic damage to the brain. Researchers have reported that Hibiscus alleviates cerebral hypoxia and also
decreases anxiety and increases memory and learning capacity. The researchers felt that based on their finding on
Hibiscus, the plant warranted further investigation as a possible tool in the treatment and prevention of various
types of dementia. Other researchers have reported that H.rosa sinensis root extracts attenuate reserpine toxicity
and reverse the elevations of SOD (superoxide dismutase), CAT (Catalase) , and GSH (glutathione reductase)
enzymes typically elevated in cerebral inflammatory diseases and damage. 30
Recently published animal studies show that Hibiscus asper species may have an anxiolytic effect due to CNS
effects involving dopaminergic pathways,26 explaining the folkloric use for depression. Another species of
Hibiscus, H. cannabinus, sometimes going by the common name Kenaf, has been shown to inhibit tyrosinase, an
enzyme involved in the synthesis of monoamines.27 Kenaf seeds are high in essential fatty acids, phytosterols, and
vitamin E, the sum of which many credit to providing anti inflammatory activity. One group of researchers
demonstrated that Kenaf seed extracts could halt the progression of early colon cancer in rat models.28 Other
researchers have repeated these findings confirming a neuroprotective effect of Hibiscus rosa sinensis.29 A
common animal research model is to induce states of cerebral hypoxia and test for agents capable of preventing
ischemic damage to the brain. Researchers have reported that Hibiscus alleviates cerebral hypoxia and also
decreases anxiety and increases memory and learning capacity. The researchers felt that based on their finding on
Hibiscus, the plant warranted further investigation as a possible tool in the treatment and prevention of various
types of dementia. Other researchers have reported that H.rosa sinensis root extracts attenuate reserpine toxicity
and reverse the elevations of SOD (superoxide dismutase), CAT (Catalase) , and GSH (glutathione reductase)
enzymes typically elevated in cerebral inflammatory diseases and damage. 30
Hibiscus Delays the Onset of Puberty in Animals
Hibiscus sabdariffa is also occasionally reported to have hormonal effects and to delay puberty when consumed
early in life. One group of researchers investigated this by giving Hibiscus enriched drinking water at several
dosage levels to lactating rats and following the nursing offspring for onset of puberty. The researchers reported
that the Hibiscus extract caused the lactating female rats to consume less food and drink than the control animals,
due to unknown mechanisms, and a decrease in corticoid levels was also observed in the treated lactating females
compared to the controls. The nursing offspring were followed for the onset of puberty and those whose mothers
were dosed with Hibiscus did show a delayed onset of puberty. 31 Researchers proposed possible alterations in
corticosterones and leptin levels of the breast milk in the treated animals might be an explanation. Other
researchers confirmed these findings reporting that Hibiscus sabdariffa will delay puberty when juvenile rats are
dosed with Hibiscus sabdariffa, and
Numerous Studies have Demonstrated Cardiovascular Benefits
Hibiscus rosa sinensis is reported to have cardioprotective effects. One group of researchers has recently reported
to have beneficial effects in helping the heart to repair and regenerate following ischemic injury.33 With
pretreatment, Hibiscus was capable of reducing infarct size in test animals and showing positive ionotropic effects.
Many studies have shown Hibiscus, like other high flavonoid plants, to have hypolipidemic effects and to help
protect the vasculature from oxidative damage. Hibiscus sabdariffa has also been demonstrated to have
hypolipidemic effects similar to what is accomplished by a 4 microgram dose of pravastatin and to have a similar
mechanism of activity inhibiting HMG CoA reductase enzyme activity.34 One human clinical study on the
hypolipidemic effects of Hibiscus reported that a dose of 1 gm of Hibiscus sabdariffa leaves per day had no
hypolididemic effects. The low dose and/or the lack of flower material may explain the lack of efficacy in this
trial.35 Other researchers dosed hyperlipidemic rats with Hibiscus, simultaneous with cholesterol feeding and
reported that both 200 mg/Kg and 300 mg per Kg of Hibiscus leaves reduced serum cholesterol by 18.5 and 22%
respectively after 4 weeks of supplementation.36 A dose of 100 mg/Kg displayed no cholesterol lowering effects.
Hibiscus roots have also been examined for possible cholesterol lowering effects. Hibiscus rosa sinensis roots
have showed a hypolipidemic effect in animals and protection against fatty liver in animal models of
hyperlipidemia.37 An isolate of Hibiscus sabdariffa polyphenols (flavonoids) was shown to be a more powerful
hypolipidemic agent than an extract of the whole plant using similar dosages. 38 Investigations into the
mechanisms of action of H.sabdariffa report reduced expression of fatty acid synthase and HMG CoA reductase
enzymes systems. Further the liver's binding of low density lipids (various LDL fractions) is enhanced by
Hibsicus polyphenols.
Hypotensive and blood pressure regulating effects have also been credited to Hibiscus. The anthocyanins in
Hibiscus have been shown to inhibit ACE (angiotensin converting enzyme) and likely contribute to the
hypotensive effects. 39 Hibiscus sabdariffa flowers prepared into a simple infusions is reported to act as a mild
hypertensive agent. One human clinical trial used Hibiscus flower tea to be helpful for adults with mild
hypertension.40

Hibiscus May Improve Blood Paramaters in Diabetes and Metabolic Syndrome

H.sabdariffa protects the vascular smooth muscle in states of high blood glucose, modulates the expression of
connective tissue growth factor and stimulation of metabolic end products or high glucose loads, sometime referred
to as "RAGE", advanced glycation end products. 41 Low density lipoprotien or LDL is known to be associated
in the formation of astherosclerotic lesions due to promotion of macrophage derived "foam cells." Hibiscus
sabdarrifa has been shown to inhibit LDL oxidation as well of the progression of atherosclerotic lesions in animal
(rabbit) studies.42 Anthocyanin rich extracts of Hibiscus sabdariffa are noted to reduce foam cell formation; One
human clinical trial involving 60 diabetic subjects evaluated the effects of Hibiscus sabdarrifa tea on lipids and
lipoproteins. Patients were randomly divided into two groups and given either Black tea or Hibiscus tea, twice
daily for a month. The patients receiving the Hibiscus tea showed significantly lower lipids, without significant
differences in lipoproteins compared to the group receiving the black tea.43

Hibiscus has Displayed Anti Venom Effects

Hibiscus aethiopicus has been shown to possess anti venom activities against several species of Naja vipers.44
Hibiscus extracts were shown to protect muscle cells against the cytotoxic effects of snake venom in rabbits and
guinea pigs against what would have otherwise been a fatal dosage of Naja venom.

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