Monday, October 14, 2019

Phyllanthus amarus Schum. & Thonn.



HERBAL

MEDICINAL





PHYLLANTHUS
Phyllanthus amarus Schum. & Thonn.




by


RETTODWIKART THENU, S.Pd















PHYLLANTHUS
Phyllanthus amarus Schum. & Thonn.


DESCRIPTION  
DESCRIPTION (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
Phyllanthus amarus Schum. & Thonn. is a small herbaceous annual plant that can grow up to 60 cm tall. Leaves are simple, alternate, green and stipulate. The blade is 3–8 mm by 2–4.5 mm and oblong-elliptic. The fruits are green, depressed globose in shape, 3-lobed and smooth. Both the flowers and fruits are borne under the branches.[1,2]
ORIGIN: Native to Mexico and South America.[3]

DESCRIPTION (Medical Economics Company, Inc. 2000)
Medicinal Parts: The whole, dried herb is the medicinal part.
Flower and Fruit: The flowers are axillary. The male flower has 5, 0.5 mm long, acute, pale-green sepals with a white margin. There are 3 stamens with the filaments forming a 0.2 mm high column. The female flowers have an apically thickened pedicle and 5 ovate-elongate, up to 1 mm long, yellowish-green sepals. The ovary is 0.3 mm in diameter and 3-chambered. The fruit is ochre to olive with 3 pressed lobes, 2 mm in diameter and 1 mm long.
Leaves and Stem: Black catnip is a monoecious, occasionally dioecious, upright or ascending herb, which grows up to 60 cm high, or occasionally higher. The bracts and stipules are linear-lanceolate, 1 mm long, cream with a brownish middle rib. The stem is round, greenish or reddish, glabrous and woody at the base.
Habitat: Africa, Asia and America.
Production: Black catnip herb is the aerial part of Phyllanthus amarus. The harvested herb is dried.
Not to be Confused With: May be confused with Phyllanthus urinaria, P, niruri, P. debilis and P. fraternus.

PHYTOCONSTITUENTS (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
Phyllanthusin D, geraniin, corilagin, elaeocarpusin, amariin, amariinic acid, amarosterol-A and B, phyllantin, hypophyllantin and others.[4–11]

MEDICINAL USES (Chevallier, A. 2018)
Parts used Whole plant
Key actions Liver protector Lowers blood sugar levels Diuretic Antiviral
Liver disease Traditional use indicates that black catnip can help in disorders such as viral hepatitis, gall bladder disease, and gallstones. A safe remedy, it is best taken on professional advice.
Viral infections Following the herb’s traditional use, black catnip makes a useful herb to combine with immunemodulating remedies such as echinacea (Echinacea spp.) in treating viral and other chronic infections.


TRADITIONAL MEDICINAL USES (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
The aerial part of the plant is used for various conditions. In Chinese medicine, the plant is made into a tea to cure kidney problems, venereal diseases, stones in the kidneys and bladder. The Malays use it to increase menstrual flow, reduce fever and cure colic. It is used by the Indians as a fish poison.[5] Indians also use the plant as liver tonic to treat liver ailments, ascites, jaundice, diarrhoea, dysentery, intermittent fever, conditions of the urogenital tract, eye disease, scabies, ulcers and wounds.[12] In Vietnam, it is used to induce sweating, and increase menstrual flow. It is also prescribed for toothache, muscle spasms and gonorrhoea. It is considered a diuretic, colic remedy and abortifacient in Southeast Asia.[5] It is also commonly used in Benin, Africa, as folk medicine against malaria.[13]

PHARMACOLOGICAL ACTIVITIES (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
Analgesic,[14] Antibacterial,[15,16] Antidiarrhoeal,[17] Antifertility,[18] Antifungal,[19] Anti-inflammatory,[20–24] Antineoplastic,[25–29] Antioxidant,[30–32] Antiplasmodial,[13,33] Antiviral,[34–39] Diuretics,[40] Hepatoprotective,[41–43] Hypoglycaemic,[11,30,44] Inhibition of gastric lesion,[22] Antimutagenic,[27,45] Insecticidal[46] and Radioprotective.[47]

PHARMACOLOGICAL ACTIVITIES
(Danladi S, Idris MA, and Umar II. 2018)
Antidiabetic activity  Ethanolic extract of Phyllanthus niruri was found to have significant antidiabetic activity in insulin-dependent diabetes mellitus rat, but showed no effect on non–insulin-dependent diabetes mellitus rat [18] . Additionally, the ethanol extract was found to lower lipid profiles (decrease in plasma cholesterol, triglycerides, Low density lipoprotein cholesterol, very low density lipoprotein cholesterol and atherogenic index, while there is increase in high-density lipoprotein cholesterol) in both insulin-dependent diabetes mellitus and non– insulindependent diabetes mellitus animals [18] . Concordantly, a one week study carried out on non-insulin dependent diabetic patients using aqueous extract of aerial parts of Phyllanthus amarus showed that, it is not effective in lowering both fasting blood glucose and postprandial blood glucose level in untreated non-insulin dependent diabetic patients [19]. Aqueous extract of Phyllanthus niruri demonstrated significant hypoglycemic activity in streptozotocininduced diabetic rats [20]. Relatedly,the methanol extract of the plant has also been found to reduce blood sugar level in alloxan-induced diabetic rats [21] .
Hyperlipidemic activity  Scientific studies have shown that Phyllanthus niruri has antihyperlipidemic effect. It was also reported that the aqueous extract exhibited antihyperlipidemic activity [20]. Hydro-alcoholic extract of leaves of Phyllanthus amarus was also found to have antihyperlipidemic potential in hyperlipidemic rats [22]. Additionally, phyllantrin which is a bioactive compound of Phyllanthus niruri was administered for twelve weeks to mice co-fed with High Fat Diet (HFD); there was protection against HFD induced weight gain and adiposity, reduced mRNA expression of adipogenic genes and increased expression of lipolytic genes in white adipose tissue, reduced liver triglyceride accumulation, restoration of HFD induced serum lipid disturbances as well as reduced serum triglycerides and free fatty acids in HFD fed mice [23] . The lipid-lowering activity of Phyllanthus niruri was found to be mediated through inhibition of hepatic cholesterol biosynthesis, enhanced catabolism of LDL, increased faecal bile acids excretion and activation of LCAT and tissue lipases [24] .
Hyperuricemic effect  It was reported that the methanol extract of the leaves of Phyllanthus niruri exhibited anti hyperuricemic activity in hyperuricemic rats. Lignans isolated from Phyllanthus niruri (Phyllanthin, hypophyllanthin, phyltetralin and niranthin) were also found to increase the urinary excretion of uric acid in hyperuricemic rat. Therefore, the uricosuric effect of this plant may be the attributed mechanism of anti hyperuricemic action [25] .
Lithiasis  Phyllanthus niruri has shown inhibitory effect against calcium oxalate crystal growth and aggregation in human urine. This medicinal plant exhibited antiurolithic activity in both in vitro and in vivo studies [6] . The aqueous extract of Phyllanthus niruri inhibits the growth of the matrix calculus as well as decrease the number of stone satellites in Wistar rats [26]. Oral administration of Phyllanthus niruri extract by calcium stone forming patients reduced urinary calcium in hypercalciuric patients [27] .
Nephroprotective effect of Phyllanthus amarus  The aqueous extract of Phyllanthus amarus at doses of 200 mg and 400 mg/kg/day for 14 days, were found to protect against the nephrotoxic effect of paracetamol and gentamicin in rat, by maintaining the level of blood urea nitrogen and serum creatinine within the normal range compared to control group [1]. In another study, the ethanol extract of the leaves of the plant was investigated for its nephroprotective activity against gentamicin induced nephrotoxicity in rats. Co-administration of the extract with gentamicin prevented kidney and improved all nephrotoxic parameters (physical, urinary and blood) observed [28]. The extracts of Phyllanthus amarus prepared by dissolving the leaves in olive oil for fourteen and seven days were tested for their ability to protect the kidney against cisplatin induced nephrotoxicity. The study revealed significant decrease
Antiplasmodial activity Ethanolic extract of Phyllanthus niruri was found to have potential anti plasmodial activity in vitro by inhibition of the developmental stage of trophozoite to schizonts [7] . Similar in vitro study also showed that the callus extract and intact Phyllanthus niruri extract inhibited the development of trophozoites to schizonts (developmental stage of Plasmodium falciparum) in a dose-dependent manner. The anti plasmodial activity of extract of Phyllanthus niruri (whole plant) exhibited a higher anti plasmodial activity than all calli and intact fresh apical stem extracts [30] . It was reported that the water extraction of Phyllanthus niruri gives better results of antiplasmodial activities than ethanolic extraction and only leaves and stems parts of the plant were active in vitro against plasmodium [31]. 1-O-galloyl-6-O-luteoylR-D-glucose isolated from the Phyllanthus niruri was found to have inhibitory effect against Chloroquine-susceptible P. falciparum strain in vitro [32]. Chloroform/ethanol extract of Phyllanthus niruri showed significant inhibition of P. falciparum growth at different concentrations [33] .
Antinematodal activity Two compounds isolated from Phyllanthus amarus, 8-(3-methyl-but2–enyl)-2-phenyl chroman-4-one and 2-(4-hydroxyphenyl)-8-(3- methyl-but-2–enyl)-chroman-4-one were found to have antinematodal activity against Meloidegyne incognita and Rotelenchulus reniformis [34] .
Antibacterial activity Phyllanthus amarus has broad spectrum antibacterial activity on both gram positive and gram negative bacteria. A study carried out on different bacterial isolates; Bacillus stearothermophilus, Staphylococcus aureus, Bacillus subtilis, Micrococcus leuteus, Salmonella typhi, Enterobacter aerogens, Proteus mirabilis, and Proteus vulgaris revealed that P. amarus showed the least MIC on all bacteria tested [35]. Similarly, the methanolic extract of Phyllanthus amarus was found to have potent inhibitory effect against drugresistant pathogenic gram-negative bacteria; Shigella spp., E. coli, V. cholerae, S. aureus, S. typhimurium, P. aeruginosa, B. subtilis, Klebsiella and Streptococcus sp. in a dose-dependent manner [36] .
Hepatoprotective effect The Protein isolate of Phyllanthus niruri indicates hepatoprotective effect against acetaminophen-induced toxicity [37]. Another study also showed that the aqueous extract of Phyllanthus niruri inhibited paracetamol induced hepatotoxicity in mice [38]. Similarly, fishes pretreated with Phyllanthus niruri extract were protected against paracetamol-induced hepatotoxicity when compared to control [39]. It was also reported that a protein isolated from Phyllanthus niruri protects against oxidative damage of hepatocytes induced by carbon tetrachloride [40]. Both aqueous and methanol extracts of Phyllanthus niruri have been demonstrated to possess hepatoprotective effect [41] . The extract of Phyllanthus amarus was also found to increase hepatic cell function [16] . Similarly, another study reported the hepatoprotective effect of Phyllanthus amarus in ethanol-induced hepatotoxicity and the effect was comparable to standard hepatoprotective drug silymarin. The hepatoprotective effect of the extract was associated with its antioxidant activity [42] . Phyllanthus amarus extract and phyllanthin isolated from the aerial part of the plant were found to protect the human hepatoma HepG2 Cell line against carbon tetrachloride induced hepatotoxicity. Phyllanthin demonstrated the hepatoprotective effect at a lower dose compared to Phyllanthus amarus extract and the effect was in a dose-dependent manner [43]. Combination of ethanolic extract of Phyllanthus amarus and silymarin gives synergistic hepatoprotective activity against carbon tetrachloride-induced hepatotoxicity. The effect was associated with higher concentration of phyllanthin. A combination of silymarin with ethanol extract provided higher hepatoprotective activity than when combined with aqueous extract [44]
Effect on Viral Infections It was reported that the extract of Phyllanthus amarus in an in vitro study inhibited DNA polymerase in Hepatitis B virus (HBV) and Woodchuck hepatitis virus (WHV). Also, in vivo study shows that the extract of Phyllanthus amarus has effect against Hepatitis B virus in infected human [45]. Another study revealed that the extract blocked enzymes that play an important role in the reproduction of hepatitis B virus [46]. Oral administration of Phyllanthus amarus was found to decrease the mortality rate and significantly increase the survival of hepatocellular carcinoma harboring animals [47]. It was also reported that an aqueous extract of Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. The extract also inhibits woodchuck hepatitis virus DNA polymerase and binds to the surface antigen of WHV in vitro [48] .It was reported that the alkaloidal extract of Phyllanthus niruri inhibited the growth of both HIV-1 and HIV-2 strains cultured on human MT-4 cells [46]. Similarly, the water alcoholic extract of Phyllanthus amarus was found to be a potent inhibitor of HIV-1 replication in HeLaCD4+ and also inhibited the RT inhibitor-resistant HIV strains. The inhibitory effect of Phyllanthus amarus against HIV strain was both in vitro and in vivo [49, 50] . Niruriside, a novel compound isolated from Phyllanthus niruri exhibited anti-HIV activity. It was found to exert inhibitory effect against the binding of REV protein to RRE RNA with an IC50 value of 3.3 µM [51] .
Effect on Reproductive system Methanol extracts of the leaves of Phyllanthus amarus lead to a decrease in sperm motility and count of male guinea pigs in a dosedependent manner. The effect was comparable to the observed effects of Vitamin E on sperm parameters [52] . The ethanolic extract of Phyllanthus amarus significantly affected the litter size and weight of Wistar albino rats at birth in a dose-dependent manner [8] . The alcohol extract of a whole plant of Phyllanthus amarus was found to show reversible antifertility effect in female mice [53]. Similarly, Phyllanthus amarus when given orally to male albino mice induced gradual inhibition of fertility potential with a decline in epididymal sperm profiles. However, the antifertility effect was reversible upon withdrawal of medicinal plant [54] . The methanolic extract of Phyllanthus amarus leaves caused significant increase in the level of testosterone of male Guinea pigs in a dose- and time- dependent manner. It also caused changes in the levels of Leutenizing (LH) and Follicle stimulating (FSH) hormones. These changes caused by Phyllanthus amarus were comparable to the changes caused by vitamin E on Leutenizing (LH) and Follicle stimulating (FSH) hormones. [4] .
Effect on Cardiovascular System It was reported that methyl brevifolincarboxylate (MB) isolated from the leaves of Phyllanthus niruri L. exerted vasorelaxant effect on the aortic rings of rat. It also antagonised the vasoconstriction effect of Norepinephrine [55]. MB was also found to have potent inhibitory effect against platelet aggregation; the effect was comparable to known inhibitor of platelet aggregation adenosine [3] . In a recent study, the aqueous extract of Phyllantus amarus was tested for its cardioprotective property against high-fructose (HF) diet induced cardiac damage in Wistar rats; the aqueous extract prevented the increase in levels of cardiac and aortic lipids i.e., total lipids, triglycerides, total cholesterol and free fatty acids and decreased phospholipids after co-administration with the HF for sixty days [56]. Yao et al. (2018) compared the diuretic effect of the ethanolic fraction of the plant (EEPA) to that of a standard drug (frusemide); the diuretic effect of EEPA was comparable to the standard with an additional benefit of not promoting kaliuresis. Furthermore, the diuretic activity was attributed, at least in part, to the involvement of prostaglandins [57] .
Analgesic, Anti-inflammatory and antiulcer activity Studies have shown that extract of Phyllanthus amarus has an antiinflammatory effect; and that it is effective in preventing persistent neuropathic pain, as well as prevent both ipsilateral and contralateral persistent nociception [58]. Another study showed that P. niruri exhibited potent systemic antinociceptive actions against two models of neurogenic pain [59] . Similarly, methanol extract of Phyllanthus amarus significantly inhibited gastric lesions induced by intragastric administration of absolute ethanol. Aqueous and methanol extracts of Phyllanthus amarus were found to have anti-inflammatory activity [60]
Radioprotective effect It was also reported that Phyllanthus amarus improved antioxidant activity in liver and blood of irradiated mice [61]. Similarly, Phyllanthus amarus prevented the genotoxic effect of radiation on mice chromosome, and it prevented the intestine from radiation induced damages as evident by decreased peroxidation level of intestinal membrane and elevated antioxidant system [62] .
Cancer and cytotoxicity Phyllanthus amarus offers protection against chemical carcinogenesis. It was reported that the aqueous extract of Phyllanthus amarus significantly inhibited hepatocarcinogenesis induced by Nnitrosodiethylamine (NDEA) in a dose-dependent manner in male Wistar rats [63] . Phyllanthus amarus extract was also found to have significant activity against chemically induced tumour. Inhibition of cell cycle regulation, topoisomerase II, P450 enzymes as well as antioxidant activity may contribute to the overall activity of the extract against carcinogenesis induced in animals and this may be relevant to human cancer as well [64]. It was reported that the extract of Phyllanthus amarus inhibited the mutagenicity produced by direct acting mutagens. It also inhibited the activation and mutagenicity of 2-acetaminofluorene (2-AAF), which in turn declined the mutagenesis and possibly carcinogenic potential. Oral administration of Phyllanthus extract was found to significantly inhibit urinary mutagenicity produced in rats by benzo- pyrene [65]. The study showed that the methanol extract of Phyllanthus amarus has Chemopreventive activity against N-methyl N’-nitro-N-nitrosoguanidine (MNNG) induced stomach cancer in Wistar rats [66]. The aqueous extract of Phyllanthus amarus has also demonstrated anti-mutagenic and antigenotoxic properties as indicated by the extracts ability to protect against the mutagenic effects of 2-aminofluorene, 2-aminoanthracene, 4-nitroquinoline-1-oxide, N-ethyl-N-nitro-nitrosogua- nidine, 2- nitrofluorene and sodium azide in test bacteria. In addition, the extract antagonizes DNA damage caused by DMN in hamster liver [67] .
Effect of Phyllanthus amarus on metabolizing enzymes (CYP P450 3A Family) Phyllanthus amarus significantly inhibits the Metabolism of CYPA5 and CYPA7 enzymes which are essential enzymes responsible for phase 1 drug metabolism. Co-administration of Phyllanthus amarus with orthodox drugs that are completely metabolized by CYP3A Family can lead to therapeutic failure, drug interaction and adverse effect since it will interferes with it metabolism [68]. Another study showed that CYP1A2, CYP2C9, CYP2D6 AND CYP3A4 enzymes were inhibited by aqueous extract of Phyllanthus amarus similarly human and rat glutathione S-transferases (GSTS) liver cytosolic enzyme was strongly inhibited by Phyllanthus amarus [69] . Similarly, in in vitro study it was also found out that the extract of Phyllanthus amarus significantly inhibited CYP1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP 1A, 2A, 2B, 2D and 3A enzymes activity, while in in vivo study indicated the activity of P450 enzymes after phenobarbitone administration elevated but oral administration of Phyllanthus amarus was found to reduce the activity [70]. The effect of Phyllanthus amarus extract on the pharmacokinetic profile of midazolam has been studied and found to interfere with CYP3A4, thereby increasing the blood level of the drug [71]. The mean maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under curve (AUC0-8), and elimination half-life (T1/2) (2.9-, 1.6-, 2.8-, and 1.4-fold, respectively) were all increased when compared to control group receiving a single oral dose of midazolam [71] .

ANTIOXIDANT  (Danladi S, Idris MA, and Umar II. 2018)
Phyllanthus niruri showed significant improvement of body antioxidant activities in both insulin and non-insulin dependent diabetes mellitus animals [18]. A protein isolated from Phyllanthus niruri has also been showed to act as radical scavenger, thereby scavenging the free radicals released by the toxic effect of carbon tetrachloride in hepatocytes. The hepatoprotective effect of Phyllanthus niruri may be associated with  it action at cellular level by reducing oxidative stress as a radical scavenger and promoting antioxidative defense mechanism of the cells [40] . In vitro antioxidant assay showed that the plant is an effective radical scavenger [62] . High phenolic content of Phyllanthus amarus showed a strong correlation with its antioxidant activity. Phyllanthus amarus has a high antioxidant activity because of its several phenolic constituents and it inhibits chromium (VI) induced oxidative toxicity to MDAMB-435S human breast carcinoma cells [76]. Similarly, it was also reported that Phyllanthus amarus has a strong free radical scavenging The Journal of Phytopharmacology 345 activity and ferric reducing property; its strong free radical scavenging activity is associated with its high phenolic content. The methanol extract of dried Phyllanthus amarus has lower antioxidant property compared to fresh sample [77] . Phyllanthus amarus was found to have effective in vivo antioxidant activity as seen by its ability to inhibit carbon tetrachloride induce lipid peroxidation in rat liver; while in vitro antioxidant activity showed that the plant has high radical scavenging activity [41] . Phyllanthin was reported to have higher radical scavenging capacity than Phyllanthus amarus, as indicated by its higher antioxidant activity than Phyllanthus amarus [43] . Phyllanthus amarus demonstrated antioxidant activities as indicated by its ability to increase the activities of enzymic and non-enzymic antioxidants and reduce malondialdehyde levels [20]. The methanol extract of Phyllanthus amarus was found to possess potential antioxidant activity as evident by its ability to inhibit lipid peroxidation and scavenge hydroxyl and superoxide radicals in vitro [21]. Aqueous extract of Phyllanthus niruri exhibited high free radical scavenging, inhibition of reactive oxygen and lipid peroxidation [39] . Phyllanthus amarus alleviated oxidative stress induced by nimesulide in the liver as evident by the outcome of post-treatment; with Phyllanthus amarus rapidly restoring most of the Nimesulideinduced oxidative changes compared to those obtained by the selfrecovery of liver [78].

DOSAGE (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
A decoction may be prepared with 10 plants in 1 L of water.[12]

DOSAGE AND SENSIBLE USE (Chevallier, A. 2018)
As with all medicines, getting the dosage right is essential. Too much and you risk overdosing, too little and the remedy may not work. Follow the guidelines on these pages to ensure that you use herbal remedies safely and appropriately.

ADULT DOSAGES
Each of the remedies listed in the A–Z of Herbal Remedies has a letter indicating its adult dosage—how much of the herb to take per day or per week.
To take an example, passion flower (Passiflora incarnata) on p.173 has C for its dosage. Looking at the dosage guide (right), it can be seen that C = 2–4g a day or 30g a week. Passion flower should therefore be taken at these recommended dosages.
As another example, hawthorn leaf (Crataegus spp.) has M and C for its dosage. M applies to manufactured products: take prepackaged hawthorn products, such as standardized tablets and capsules, at the manufacturer’s recommended dosage. C applies to dried hawthorn leaf or berry: take at the recommended daily or weekly dosage, i.e. 2–4g a day or 30g a week.
Similarly, each of the other letters gives specific recommendations on how to use the herb.
Teas and decoctions The dosages given in the guide apply when making teas and decoctions from dried herb material—bark, leaves, roots, etc. For fresh herb material you can use 11⁄2–2 times the quantity of dried material.
Tinctures It is not possible to give clear guidelines for tinctures owing to the wide variation in their strength. Ask advice on dosage when purchasing a tincture. In general, the dosage range for a 1:3 tincture is the same (in milliliters not grams) as the above dosages, i.e. for A, the dosage of a 1:3 tincture is 5–15ml a day.

ADULT DOSAGE GUIDE
Recommended ADULT dosage as given in the key information boxes (see opposite page). For children and people over 70, see below and opposite.
Ø  A = 5–15g a day, or max. 100g (31⁄2 oz) per week
Ø  B = 3–7.5g a day, or max. 50g (2 oz) per week
Ø  C = 2–4g a day, or max. 30g (1 oz) per week
Ø  D = 1–2g a day, or max. 15g (1⁄2 oz) per week
Ø  M = Take product at manufacturer’s recommended dosage.
Ø  T = Topical application on the skin only (Note: preparations made specifically for topical use should not be taken internally.)

Powders Take the minimum recommended daily dosage only.
Tablets and capsules Take at the manufacturer’s recommended dosage.

CHILDREN’S DOSAGES
Do not give babies under 6 months any medication without professional advice.
You may need to adjust dosage levels for children who are particularly small or large for their age.
§  From 6 months to 1 year: give 1⁄10 the minimum adult dose
§  From 1 to 6 years: give 1⁄3 the minimum adult dose
§  From 7 to 11 years: give 1⁄2 the minimum adult dose
§  From 12 to 16 years: give the low adult dose.

DOSAGES FOR OVER 70s
As we age, our bodies become less efficient at breaking down drugs, including herbs. From the age of about 70 onward it is advisable to take slightly lower doses: 80 percent of the standard adult dose is normally recommended. In very old and frail
people the dosage may need to be as low as 50 percent of the standard adult dosage.

GENERAL CAUTIONS
v  Do not take essential oils internally unless on advice of a suitably qualified health care professional.
v  Do not give herbs to babies under 6 months old.
v  Do not exceed the recommended dosage levels.
v  If you are taking drugs prescribed by your doctor or hospital, check with them, or with a registered herbal or naturopathic practitioner, before taking a herbal remedy.
v  People known to have allergies should start by taking a low dose and, if this is fine, then increase the dose.
v  Contact allergy can occur on handling fresh or dried herbs. Where such allergy occurs, do not take the remedy internally. Some people are allergic to specific plant families, for example the daisy (Asteraceae) family. Several herbs listed in this book, including chamomile (Chamomilla recutita), echinacea (Echinacea spp.), and feverfew (Tanacetum parthenium), belong to this family and are known to cause contact allergy in sensitive individuals.


KEY INFORMATION (Chevallier, A. 2018)
Every remedy in the A–Z features a key information box that provides essential data on the herb. At the top, each herb is rated using a 5-star rating system, with 5 black stars = most. This gives some idea of the herb’s:
v  overall safety record (Safety)
v  long-standing use in traditional medicine (Traditional use)
v  evidence of effectiveness, as supported by scientific research (Research).
On the line below (Best taken as), suitable types of preparation are recommended; for example, yarrow (Achillea millefolium) is best taken as a tea, which gets 3 checks. Dosage information is provided on the following line. Some entries include an “Often used with” recommendation. The last and most important section lists known cautions for the remedy, and should be read carefully, especially before taking a remedy.


PREGNANCY AND AFTER
Herbal medicine has an important role to play as part of a natural approach to health care for expectant mothers and their children. While caution is required in avoiding potentially harmful remedies, many gentle-acting herbs can safely be used during pregnancy and beyond.

Herbal Medicines Pre- and Postnatally
Herbal remedies can be safe to take during pregnancy, although for the first three months of pregnancy, they should be taken only after consulting a professional. From the fourth month onward, a range of safe and effective remedies may be used to treat simple health problems such as colds and constipation. Select remedies with a long history of use in pregnancy and with no evidence of risk to mother or baby. The box below gives examples. Check labels of herbal products carefully, especially where herbs and other constituents are combined together. Alcohol should be avoided during the first three months, even in the small amounts present in tinctures. It is much better to use teas, decoctions, tablets, or capsules.

HERBS TO AVOID
Some of the herbs included in this book are contraindicated and unsafe to take during pregnancy and while breastfeeding. In particular, do not take:


• Chiretta (Andrographis paniculata)
• Neem (Azadirachta indica)
• Goldenseal (Hydrastis canadensis)
• Lobelia (Lobelia inflata)
• Butterbur (Petasites hybridus)
• Pau d’arco (Tabebuia impetiginosa)
• Coltsfoot (Tussilago farafara).

Essential oils, and herbs that contain strong essential oils such as eucalyptus (Eucalyptus spp.), thuja (Thuja occidentalis), and sage (Salvia officinalis), are also contraindicated and should not be used during pregnancy and while breastfeeding.

SOME HERBS COMMONLY USED IN PREGNANCY AND WHILE BREASTFEEDING
When pregnant and while breastfeeding, check the relevant cautions before taking a remedy. Remember that herbs are passed on to the baby in breast milk.

          Garlic (Allium sativum)
          Calendula (Calendula officinalis)
          Senna (Cassia spp.)
          Chamomile (Chamomilla recutita)
          Echinacea (Echinacea spp.)
* Raspberry leaf (Rubus ideaus)
          Butcher’s broom (Ruscus aculeatus)
          Elderflower/berry (Sambucus nigra)
          Limeflowers (Tilia spp.)
          Nettle (Urtica dioica)
          Slippery elm (Ulmus rubra)
          Bilberry (Vaccinium myrtillus)
          Cramp bark (Viburnum opulus)
          Ginger (Zingiber officinale)
          Cornsilk (Zea mays)
*Take raspberry leaf

only in the last 3 months of pregnancy; see also p.191.

Herbal Medicines and Children
By and large children respond very well to herbal remedies, even if the taste can make administering them a bit of a struggle! Adding honey or mixing with apple juice will usually help make remedies more palatable. Tablets or capsules can usually be opened and ground up and taken on a spoon mixed with honey, maple syrup, and so forth.
Children typically fall ill and recover quickly. This can be very alarming for parents, since a healthy child at 8:00 a.m. can be a very unwell one by 11:00 a.m. The main worry in acute illness is controlling fever and keeping the temperature below 102ºF (39ºC).
Children with fevers approaching this level (and above) need medical attention. That being said, the very unwell child at 2:00 p.m. can be running around again by 6:00 p.m.; children bounce back.  Get to know your child’s typical pattern when falling ill—you will often be able to recognize the difference between day-to-day problems and a potentially serious illness.
The former can be safely treated with herbal remedies, while the latter needs professional advice and treatment.  If in doubt, always err on the side of caution and seek advice.

SOME HERBAL REMEDIES SUITABLE FOR CHILDREN
Guidelines on dosage levels for children are given in Dosage and sensible use, pp.44–45.

          Garlic (Allium sativum)
          Marshmallow (Althea officinalis)
          Caraway (Carum carvi)
          Chamomile (Chamomilla recutita)
          Echinacea (Echinacea spp.)
          Californian poppy (Eschscholzia californica)
          Cinnamon (Cinnamonum verum)
          Eyebright (Euphrasia officinalis)
          Meadowsweet (Filipendula ulmaria)
          Sea buckthorn (Hippophae rhamnoides)
          Elecampane (Inula helenium)
          Plantain (Plantago spp.)
          Blackcurrant (Ribes nigra)
          Yellow dock (Rumex crispus)
          Elderflower/berry (Sambucus nigra)
          Thyme (Thymus vulgaris)
          Linden flowers (Tilia spp.)
          Red clover (Trifolium pratense)
          Slippery elm (Ulmus rubra)
          Nettle (Urtica dioica)


TIPS FOR HOME USE
Self-treatment of minor health problems makes sense and, besides helping one to feel better, can be very satisfying. These pages give a few tips on how to refine the use of herbal remedies. In cases of more serious illness, it is wise to consult a qualified herbal practitioner.

How to choose the right remedy
·         Decide what the main symptoms are.
·         Select remedies that are known to help these symptoms, for example, cranberry (Vaccinium macrocarpon) for cystitis and elderflower (Sambucus nigra) for colds and sinus congestion.
·         Develop experience using specific remedies and build up your own stock of herbal remedies.

HOW MANY TO USE
·         Combining 2–4 herbal remedies together can prove more effective, particularly if the problem is stubborn or recurs frequently; for example, recurrent cystitis infection may be treated with cranberry, plus remedies such as buchu (Barosma betulina), echinacea (Echinacea spp.), and cornsilk (Zea mays).
·         Combine remedies as teas or tinctures, or purchase a product containing the required remedies.

WHEN AND HOW MUCH TO TAKE
·         Herbal remedies are generally best taken with water about 30 minutes before a meal.
·         Take the recommended daily amount in 2–3 divided doses, ideally before your breakfast, lunch, and evening meal.
·         Moderate to high doses of an herb can be taken for a few days for minor acute problems, for example, if you are experiencing a sudden onset of cystitis symptoms, take cornsilk at the upper end of its dosage range (10–15g a day) for 3–4 days.
·         Low to moderate doses should be used for long-term problems, for example, in the case of chronic bladder irritation, take cornsilk regularly at a low dosage (5–7.5g a day).

HOW LONG TO TAKE FOR
·         Self-limiting conditions such as a sore throat or stomach upset that are safe to treat at home should clear within 10–14 days at the most. If you are not fully recovered by then, see your health care practitioner.
·         Start treatment as soon as possible, before symptoms become full-blown.
·         Some remedies may be taken long term to prevent or treat chronic illness, for example, ginkgo (Ginkgo biloba) to maintain healthy mental function or boswellia (Boswellia serrata) to provide relief for arthritic pain and stiffness.

When to seek professional advice
• Do not put off getting professional advice when symptoms are worrying, especially if severe pain or a temperature of over 102°F (39°C) are present, or if symptoms deteriorate sharply or unexpectedly. Professional advice, including telephone help lines, will help ensure that you have the right treatment at the right time.
• More detailed guidance on when to seek professional advice is given in Common Health Problems, pp.256–275.

HOW CAN AN HERBAL PRACTITIONER HELP?
• Herbal practitioners are trained to use their in-depth knowledge of herbal medicine to assess and treat a wide range of  health problems. They are able to give detailed advice on the best remedies and products to use, together with appropriate advice on diet and lifestyle. Where appropriate, they will refer to other practitioners, including medical doctors, and can advise on interactions between herbs and drugs.
• If you have ongoing health problems, or want access to natural health care for your family, contact herbal practitioners in your area and find one with whom you feel comfortable and  you trust. Check that your practitioner, or medical herbalist, is insured and a member of a professional body such as the American Herbalists Guild. He or she should provide you with details of likely costs of initial and follow-up consultations and herbs.

WHAT HEALTH PROBLEMS DO HERBALISTS TREAT BEST?
Herbal practitioners specialize in treating health problems with herbal medicine and give advice on diet and supplements. The following types of conditions often benefit from treatment:
·         allergies
·         anxiety and stress-related problems
·         arthritic and rheumatic conditions
·         chronic infection and fatigue
·         chronic inflammatory diseases
·         mild to moderate depression
·         digestive complaints
·         menstrual and menopausal problems
·         skin disorders

Herbal Dispensary
Medical herbalists stock a wide range of medicines. Each patient receives an individually tailored prescription, normally dispensed on the spot.S

HOW TO BUY REMEDIES
When buying a remedy, select a suitable herb or combination of herbs for your health problem, such as feverfew (Tanacetum parthenium) for migraine headaches. Decide how you want to take it, for example, as a capsule, and compare the different products available.
Where to obtain herbal remedies
Most people working with herbal medicine recommend buying remedies from a reputable health food shop or pharmacy. Try to find a shop that specializes in natural medicines, where the staff is knowledgeable and receives regular in-house training. Their advice can help to guide you toward buying appropriate, good-quality remedies. Shops that sell dried herbs and dispense tinctures are likely to have the most knowledgeable staff and should be actively concerned to supply goodquality herbal produce.
Do not be afraid to ask how they can be sure that the products they sell are of good quality. Buying remedies from an herbal practitioner is also a reliable way of obtaining them. He or she will stock products from growers and suppliers with a long-established record of quality control. Remember that the ethical code of a professional herbalist prevents him or her from selling you an herbal remedy without a consultation, for which you will usually have to pay. This is to assess your state of health and ensure that you receive the right advice and treatment for your situation.
However, you will probably find that herbs supplied by a practitioner compare favorably in cost and quality with herbs obtained elsewhere. Of course, you can also buy herbal remedies online. In some cases, you can source innovative products that are hard to find in a local health food shop. However, it can be very hard to distinguish between suppliers of genuine products and those that are there for the quick sale. Some mail-order and Internet companies deliberately base themselves in countries where proper quality control can be bypassed.
Where they are available, choosing organically certified herbal medicines makes sense on several counts, as plants are grown free of pesticides and pollutants, sites are regularly inspected, and the harvesting of organic herbs supports conservation in the wild.

QUALITY AND VALUE FOR MONEY
The price of herbal remedies is directly linked to quality. As a general rule, buy remedies produced by specialist herbal companies or wellknown manufacturers, where effective quality control should be routine. Retailers who consistently market remedies at prices lower than the norm are either taking a loss or selling products of doubtful quality!
The best-value remedies are often sold at middle-of-the-road prices, reflecting acceptable quality. In some cases, for example, ginseng (Panax ginseng), genuine high-quality products are available, and the higher price reflects this. Sadly, poor-quality herbal products are still commonplace. If you take St. John’s wort (Hypericum perforatum) for mild to moderate depression, for example, it is reasonable to expect some signs of improvement. If no change occurs, this might be due to poor quality. Try a different product, perhaps a tea or tincture, instead.

What the label should tell you
Different countries have different regulations governing what can (or cannot) be put on product labels. Nevertheless, any herbal product worth buying should have the information shown in the example below printed on the label or included as an insert:

BUYING DRIED HERBS
If you are purchasing dried plant material, bear in mind that herbs will soon deteriorate if they are not stored properly:
·         Herbs should be stored in clear glass jars or brown paper bags and kept out of direct sunlight and away from damp or heat.
·         Good-quality herbs should have their distinctive smell and taste— for example, marigold should be a vibrant orange color, nettle leaf a deep dark green.
·         Old or poorly dried herbs will be faded and will have lost their normal color.
·         Do not buy dried herbs in greater quantity than you need.
·         For the pros and cons of different herbal preparations, see Types of herbal remedy on pp.30–33. In general, you should select herbal remedies that provide all this information; avoid buying products on which it is lacking. In particular, do not buy products where neither the local nor the botanical names of the herbs are given.

ADVERSE REACTIONS (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
No known side effects with therapeutic dosages.[12]

TOXICITY (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
Non-toxic to mice at a dose of 100 mg/kg body weight[18] but at doses of 400 mg/kg, 800 mg/kg and 1000 mg/kg body weight in rats.[48]

TOXICITY STUDY (Danladi S, Idris MA, and Umar II. 2018)
Toxicity study of aqueous extract of Phyllanthus amarus showed that the extract can cause anaemia because it is associated with decrease in the red blood cell (RBC) count, packed cell volume (PCV), haemoglobin concentration (Hb) level of alanine aminotransferase (ALT); but there is an increase in the white blood cell (WBC) count, levels of aspartate aminotransferase (AST), total conjugated bilirubin, total protein and albumin. The extract also causes a decrease in body weight of laboratory animal. Histopathology study has shown that the kidney, liver and testes are affected by the plant; these showed the toxic potential of the plant [72]. The fractions of Phyllanthus amarus obtained from chromatographic separation showed that the plant has toxic effect on blood products [73]. Single oral dose and sub-acute toxicity study of Phyllanthus amarus showed that the medicinal plant is non-toxic with an LD50 > 5 g/kg; which is a clear indication that it is safe, but associated with slight cytotoxic effect to the human adenocarcinoma cell line [75].
The difference between this study and that of Adedapo et al. (2005a72 & b)73 may be as a result of variation in experimental condition and procedure. However, Singh et al. (2016) reported an LD50 of 2590.984 mg/Kg bw in Swiss albino mice model in laboratory condition when administered with aqueous extract of the plant. Doses above 2500 mg/Kg bw demonstrated a statistically signification elevation of urea level and histopathological changes were observed; with no significant increase in creatinine level [76] . Another study showed that alcohol extract of the whole plant was not toxic as it displayed no effect on blood cell counts, Hb levels and serum biochemical parameters. Moreover, the body weights of test animals were affected by the extract [53, 54] .


CONTRAINDICATIONS (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
No information as yet.

DRUG-HERB INTERACTIONS (Ling, K.H., Kian, C. T., Hoon, T.C. 2009)
An alcoholic extract of P. amarus was found to inhibit cytochrome P450 enzymes both in vivo as well as in vitro.[48]




REFERENCE

Chevallier, A. 2018. Herbal Remedies Handbook. DK Publishing. New York.

Danladi S*, Idris MA, Umar II. 2018. Review on pharmacological activities and phytochemical constituents of Phyllanthus niruri (Amarus). The Journal of Phytopharmacology 2018; 7(3): 341-348 Online at: www.phytopharmajournal.com  ISSN 2320-480X JPHYTO 2018; 7(3): 341-348 May- June Received: 09-03-2018 Accepted: 26-04-2018 © 2018, All rights reserved

Ling, K.H., Kian, C. T., Hoon, T.C. 2009. A Guide to Medicinal Plants - An Illustrated, Scientific and Medicinal Approach. World Scientific Publishing Co. Pte. Ltd. 5 Toh Tuck Link, Singapore 596224. Singapore.

Medical Economics Company, Inc. 2000. PDR for Herbal Medicines". Medical Economics Company, Inc. at Montvale, NJ 07645-1742.

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