Potent antihypertensive activity of Thai-Lanna medicinal plants and recipes from “MANOSROI III” database

Figures & data

Table 1. Compositions, percentage yields (%) and physical characteristics of the 30 antihypertensive recipes selected from the “MANOSROI III” database.

Recipe	Example of plants	Percentage yield (%)	Color of the extracts	Solubility in water
HT001	Cassia fistula, Cyperus rotundus, Lawsonia inermis, Nigella sativa, Asclepias curassavica, Anethum graveolens, Cassia siamea, Eugenia aromatic, Diospyros decandra, Dracaena loureiri. Glycyrrhiza glabra, Mimusops elengi, Zingiber officinale, Zingiber cassumunar	17.12	Brown	Soluble
HT002	Aegle marmelos, Plumbago zeylanica, Zingiber officinale, Piper ribesioides, Piper longum	20.26	Dark brown	Soluble
HT003	Plumbago zeylanica, Piper longum, Coriandrum sativum, Mesua ferrea	16.89	Brown	Soluble
HT004	Allium sativum, Piper nigrum, Piper longum, Kaempferia galangal	21.39	Brown	Soluble
HT005	Allium sativum, Piper nigrum, Zingiber officinale, Piper longum	27.87	Brown	Soluble
HT006	Kaempferia galangal, Phyllanthus emblica, Chrysopogon zizanioides, Nelumbo nucifera, Terminalia chebula, Zingiber officinale	21.98	Brown	Soluble
HT007	Piper nigrum, Piper longum, Kaempferia roscoeana, Acorus calamus	21.43	Brown	Soluble
HT008	Alpinia galanga, Piper nigrum, Piper longum, Kaempferia roscoeana	16.08	Brown	Soluble
HT009	Lawsonia inermis, Zingiber officinale, Piper nigrum, Piper longum	15.29	Light brown	Soluble
HT010	Piper longum, Cyperus rotundus, Coriandrum sativum, Acorus calamus	22.90	Brown	Soluble
HT011	Piper nigrum, Piper longum, Zingiber officinale	32.20	Creamy white	Soluble
HT012	Alpinia galangal, Zingiber officinale, Piper longum, Piper ribesioides	16.32	Brown	Soluble
HT013	Zingiber officinale, Piper longum, Cyperus rotundus. Glycyrrhiza glabra	24.42	Brown	Soluble
HT014	Piper nigrum, Zingiber officinale	25.82	Red brown	Soluble
HT015	Piper ribesioides, Solanum trilobatum, Citrus aurantifolia	9.68	Red brown	Soluble
HT016	Allium sativum, Cassia fistula, Zingiber officinale, Capsicum frutescens, Blumea balsamifera, Alpinia officinarum	20.54	Brown	Soluble
HT017	Piper longum, Piper nigrum	11.53	Red brown	Soluble
HT018	Combertum extensum, Piper ribesioides, Citrus aurantifolia, Solanum trilobatum	10.67	Red brown	Soluble
HT019	Allium sativum, Piper longum, Piper nigrum, Cyperus rotundus	25.29	Brown	Soluble
HT020	Zingiber officinale, Piper longum, Eugenia aromatica	25.04	Yellowish brown	Soluble
HT021	Zingiber officinale, Piper nigrum, Saccharum officinarum	22.97	Light brown	Soluble
HT022	Boesenbergia rotunda, Allium sativum, Alpinia galangal, Zingiber officinale	29.12	Dark brown	Soluble
HT023	Azima sarmentosa, Diospyros decandra, Citrus aurantifolia, Nelumbo nucifera, Zingiber cassumunar	11.89	Red brown	Soluble
HT024	Plumbago zeylanica, Piper nigrum, Cyperus rotundus, Vitex tritolia, Moringa oleifera	22.26	Dark brown	Soluble
HT025	Plumbago zeylanica, Piper nigrum, Zingiber officinale, Oryza sativa, Croton crassifolius	18.67	Brown	Soluble
HT026	Tiliacora triandra, Harrisonia perforate, Tinospora crispa, Cassia siamea, Nelumbo nucifera, Ficus racemosa, Artocarpus heterophyllus, Mesua ferrea, Mimusops elengi, Capparis micracantha	13.59	Red brown	Soluble
HT027	Diospyros decandra, Dracaena loureiri	8.46	Yellow	Soluble
HT028	Alpinia galangal, Zingiber officinale	15.67	Dark brown	Soluble
HT029	Piper longum, Citrus aurantifolia, Allium sativum	27.97	Dark brown	Soluble
HT030	Spondias mombin, Zingiber cassumunar, Saccharum officinarum	20.72	Light brown	Soluble

Table 2. Percentage changes of the mean arterial blood pressure (MABP), heart rate (%) and duration of action of the aqueous extracts of 30 selected recipes evaluated with the l-NAME-induced hypertensive rat model in comparison with the standard drug, prazosin hydrochloride.

		Intra-arterial BP (mm Hg)		Percentage changes of MABP (%)			Heart rate (bpm)		Percentage changes of the heart rate (%)
				Decrease
Recipes	Doses (mg/kg)	Before extract administration	After extract administration	Percentage changes	Folds of prazosin	Increase	Before extract administration	After extract administration	Decrease	Increase	Duration of action (s)
HT001^a	7.10	122.83 ± 4.01	94.17 ± 4.87	23.33 ± 2.94	2.07	–	226.67 ± 5.58	266.67 ± 13.33	–	1.57 ± 3.32	749.17 ± 138.28
HT002	8.40	133.47 ± 5.05	174.84 ± 8.28	–	–	31.00 ± 13.98	246.88 ± 10.89	234.54 ± 17.76	5.00 ± 2.92	–	249.00 ± 208.08
HT003	7.00	127.78 ± 3.77	142.15 ± 5.34	–	–	11.25 ± 6.34	255.43 ± 12.25	237.55 ± 9.05	7.00 ± 4.24	–	103.75 ± 45.34
HT004	8.90	139.83 ± 7.64	124.50 ± 7.90	9.17 ± 1.72	0.82	–	267.50 ± 20.23	251.33 ± 16.76	10.17 ± 1.19	–	203.00 ± 87.94
HT005	11.50	135.83 ± 8.06	117.50 ± 7.31	13.50 ± 1.89	1.20	–	265.00 ± 11.18	252.50 ± 15.10	6.00 ± 1.84	–	384.17 ± 185.42
HT006	9.20	124.90 ± 2.45	151.13 ± 6.76	–	–	21.00 ± 5.00	267.98 ± 19.73	289.42 ± 16.90	–	8.00 ± 1.73	260.00 ± 183.30
HT007	8.90	137.55 ± 6.54	159.56 ± 5.10	–	–	16.00 ± 7.90	233.12 ± 13.75	241.98 ± 12.09	–	3.80 ± 2.80	1641.00 ± 3173.38
HT008	6.70	141.33 ± 2.36	123.17 ± 2.83	13.33 ± 1.33	1.18	–	253.33 ± 22.12	235.00 ± 19.79	7.00 ± 1.29	–	332.50 ± 129.87
HT009	6.40	134.67 ± 4.22	123.33 ± 4.56	8.33 ± 1.02	0.74	–	278.33 ± 24.82	258.33 ± 20.40	6.50 ± 1.71	–	147.00 ± 80.33
HT010	9.50	138.67 ± 5.09	169.16 ± 2.12	–	–	15.50 ± 0.71	247.89 ± 8.87	199.55 ± 8.13	19.50 ± 23.33	–	90.00 ± 42.43
HT011	13.40	126.75 ± 1.99	145.34 ± 4.82	–	–	14.67 ± 7.57	288.67 ± 6.48	307.92 ± 21.77	–	6.67 ± 4.62	203.33 ± 150.44
HT012	6.80	141.32 ± 2.13	167.46 ± 3.98	–	–	18.50 ± 7.55	254.90 ± 15.44	220.49 ± 11.45	13.50 ± 6.56	–	153.75 ± 178.48
HT013	10.20	127.81 ± 4.47	146.72 ± 7.17	–	–	14.80 ± 7.92	277.14 ± 13.22	241.11 ± 13.34	13.00 ± 3.67	–	96 ± 116.96
HT014	10.80	140.77 ± 4.86	169.98 ± 4.80	–	–	20.75 ± 16.68	229.27 ± 9.87	118.00 ± 7.44	18.00 ± 19.44	–	97.50 ± 45.00
HT015	4.00	132.89 ± 3.59	151.49 ± 3.87	–	–	14.00 ± 4.97	263.21 ± 11.35	239.52 ± 14.98	9.00 ± 2.00	–	97.50 ± 15.00
HT016^a	8.60	134.17 ± 5.56	97.00 ± 3.34	27.17 ± 3.17	2.42	–	280.00 ± 8.56	256.67 ± 7.15	8.17 ± 1.58	–	335.00 ± 136.91
HT017	4.80	139.79 ± 6.98	153.77 ± 5.74	–	–	10.00 ± 7.81	237.87 ± 17.57	226.76 ± 10.17	4.67 ± 4.04	–	135.00 ± 25.98
HT018	4.40	142.54 ± 2.11	192.43 ± 1.63	–	–	35.00 ± 13.53	291.11 ± 21.63	318.27 ± 15.87	–	9.33 ± 9.24	325.00 ± 251.15
HT019	10.50	129.76 ± 4.87	145.98 ± 5.00	–	–	12.50 ± 4.20	282.31 ± 17.54	290.78 ± 13.76	–	3.00 ± 2.00	285.00 ± 185.74
HT020	10.40	133.83 ± 2.50	114.50 ± 4.10	14.50 ± 2.42	1.29	–	298.33 ± 9.46	292.50 ± 13.89	7.50 ± 1.18	–	64.67 ± 23.87
HT021	9.60	133.47 ± 7.55	157.93 ± 6.41	–	–	18.33 ± 2.52	269.59 ± 11.44	289.35 ± 12.55	–	7.33 ± 1.15	80.00 ± 48.22
HT022	12.10	129.88 ± 5.91	157.15 ± 3.66	–	–	21.00 ± 4.36	247.98 ± 12.24	267.00 ± 12.88	–	7.67 ± 5.13	193.33 ± 41.63
HT023^a	5.00	137.67 ± 4.66	104.00 ± 3.37	24.00 ± 1.75	2.13	–	290.00 ± 3.42	290.83 ± 6.64	–	6.00 ± 1.24	509.27 ± 207.91
HT024	9.30	136.91 ± 4.79	157.99 ± 3.75	–	–	15.40 ± 8.08	266.88 ± 16.67	278.96 ± 4.91	–	4.60 ± 1.52	215.00 ± 165.38
HT025	7.80	137.67 ± 3.33	122.33 ± 4.59	8.00 ± 1.53	0.71	–	255.00 ± 17.65	231.67 ± 17.40	9.00 ± 0.93	–	83.33 ± 55.61
HT026	5.70	132.53 ± 8.52	147.90 ± 2.31	–	–	11.60 ± 6.35	283.75 ± 4.84	260.48 ± 16.33	8.20 ± 6.57	–	387.00 ± 194.54
HT027	3.50	147.17 ± 3.41	127.17 ± 5.24	13.66 ± 2.16	1.21	–	265.00 ± 8.06	266.67 ± 7.15	–	5.67 ± 0.76	131.67 ± 94.00
HT028	6.50	144.86 ± 4.57	151.74 ± 8.32	–	–	4.75 ± 2.22	230.85 ± 18.45	218.15 ± 9.60	5.50 ± 3.11	–	266.25 ± 236.34
HT029^a	11.70	143.00 ± 2.52	119.50 ± 1.45	16.50 ± 0.99	1.47	–	292.50 ± 12.37	296.67 ± 8.03	–	6.33 ± 0.76	50.17 ± 14.30
HT030^a	8.60	123.50 ± 3.55	99.67 ± 3.46	19.33 ± 1.78	1.72	–	255.00 ± 15.86	228.33 ± 14.00	10.00 ± 2.80	–	250.83 ± 101.89
Prazosin hydrochloride	2.00	128.66 ± 2.38	114.18 ± 2.15	11.25 ± 1.72	–	–	241.95 ± 10.01	249.45 ± 11.52	–	3.10 ± 5.05	>1 hr

^aSignificant difference in comparing to prazosin hydrochloride (p < 0.05).

The administration doses of each recipe extract was calculated based on the traditional use of the recipes as a pill according to the following equation:

where, the weight of 1 pill is about 1 g. Dose translation factor from human to rat calculated from the Km factor, body weight (kg) divided by body surface (m²) is 25 (Reagan-Shaw et al., 2008). The bioavailability of the oral administration was approximately equal to 10% according to the reported average oral bioavailability of water-soluble biologically active constituents in plants (Bhattacharya & Ghosh, 2009; Manach et al., 2004).

Table 3. Percentage yield, percentage decrease of the mean arterial blood pressure (MABP), heart rate change and duration of action of the aqueous extracts of the 10 selected plants evaluated with the l-NAME-induced hypertensive rat model in comparison with the standard antihypertensive drug, prazosin hydrochloride.

			Decrease of MABP (%)
No.	Extract	Percentage yield (%)	% decrease	Folds of prazosin hydrochloride	HR change (%)^b	Duration of action (second, s)
1	Cassumunar ginger (Zingiber cassumunar)	29.19	39.83 ± 3.92^a	3.54	(+)11.50 ± 4.33	180.00 ± 88.99
2	Garlic (Allium Sativum)	65.17	35.83 ± 3.79^a	3.18	(−)8.00 ± 1.03	362.50 ± 117.37
3	Ginger (Zingiber officinale)	26.94	21.00 ± 2.56^a	1.87	(+)8.33 ± 1.17	490.00 ± 118.66
4	Galangal (Alpinia galanga)	21.35	17.67 ± 3.38	1.57	(+)9.50 ± 2.74	287.50 ± 114.46
5	Indian long pepper (Piper chaba)	16.25	17.17 ± 1.35	1.53	(−)8.83 ± 3.04	316.67 ± 96.63
6	Pepper (Piper nigrum)	8.01	16.33 ± 1.52	1.45	(−)7.83 ± 1.70	183.33 ± 90.36
7	Myrobalan wood (Terminalia chebula)	17.68	16.17 ± 2.94	1.44	(+)7.83 ± 2.12	220.83 ± 119.95
8	Szechwan lovage rhizome (Ligusticum chuanxiong)	40.05	13.33 ± 1.77	1.84	(−)4.17 ± 2.06	84.17 ± 55.35
9	Golden shower (Cassia fistula)	7.29	10.17 ± 1.28	0.90	(−)9.17 ± 2.99	25.83 ± 4.36
10	Myrtle grass (Acrous calamus)	18.35	10.00 ± 1.06	0.89	(−)8.50 ± 0.92	24.17 ± 3.75
11	Prazosin hydrochloride (2 mg/kg)	–	11.25 ± 1.72	1	(+)3.10 ± 5.05	>1 h

^a= significant difference from the standard drug (p < 0.05), ^b(+) = increase, (−) = decrease.

Table 4. Percentage yield (%), dose (mg/kg), percentage decrease of the mean arterial blood pressure (MABP), heart rate change (%) and duration of action of the extracted fractions of cassumunar ginger (Zingiber cassumunar), garlic (Allium Sativum) and ginger (Zingiber officinale) in the l-NAME-induced hypertensive rat model.

				Decrease of MABP (%)
Extract	Fraction	Percentage yield (%)	Dose (mg/kg)	% decrease	Folds of prazosin hydrochloride	% HR change^b	Duration of action (second, s)
Cassumunar ginger  (Zingiber cassumunar)	Water (F1)	43.20	4.32	10.83 ± 0.87	0.92	(−)4.67 ± 0.82	22.76 ± 3.33
	Butanol (F2)	21.12	2.11	17.67 ± 3.16^a	1.57	(+)5.83 ± 1.38	80.00 ± 26.46
	Ethyl acetate (F3)	10.59	1.06	12.67 ± 1.83	1.13	(−)1.50 ± 0.67	31.67 ± 6.54
Garlic (Allium sativum)	Water (F4)	62.55	6.26	27.17 ± 1.83^a	2.42	(−)7.00 ± 1.30	232.50 ± 74.87
	Butanol (F5)	3.275	0.33	13.83 ± 2.34	1.23	(−)3.33 ± 0.56	132.50 ± 48.13
	Ethyl acetate (F6)	2.67	0.27	20.33 ± 1.69^a	1.81	(+)0.50 ± 0.50	107.50 ± 62.74
Ginger (Zingiber officinale)	Water (F7)	62.31	6.23	12.33 ± 1.38	1.09	(+)2.17 ± 2.17	108.33 ± 86.43
	Butanol (F8)	6.49	0.65	18.00 ± 1.63^a	1.60	(+)4.67 ± 0.84	127.50 ± 44.12
	Ethyl acetate (F9)	4.18	0.42	15.67 ± 1.11	1.39	(+)3.00 ± 1.03	36.67 ± 5.87
Prazosin hydrochloride	–	–	2	11.25±1.72	1	(+)3.10 ± 5.05	>1 h

^a= significant difference from the standard drug (p < 0.05), ^b(+) = increase, (−) = decrease.

Doses of each extract were calculated from the amount of the recipes administration as the traditional bolus dose as follows: Dose (mg/kg) = [% yield of the extract (g/100 g)/60 (average human BW, Kg)] × 25, where, the weight of 1 pill is about 1 g. The tolerance in rats was equal to 25-times of human. The bioavailability of the oral administration was approximately equal to 10%.

Table 5. Phytochemical constituents of the top 5 aqueous recipes extracts selected from the “MANOSROI III” database.

	Phytochemical constituents^a
				Glycoside
Recipes	Triterpene	Alkaloid	Anthraquinone	F	G	S	Flavonoid	Carotenoid	Tannin	Xanthone
HT 001	−	−	−	+	−	+	−	−	−	+
HT 016	−	+	−	+	−	+	−	−	−	−
HT 023	−	−	−	+	−	+	−	−	−	+
HT 029	−	+	−	+	−	+	−	−	−	−
HT 030	−	+	−	+	−	+	−	−	−	+

^a + = presence, − = absence.

Table 6. Phytochemical constituents of the 10 selected single plant extracts from the 12 antihypertensive medicinal plant recipes.

	Phytochemical constituents^a
				Sugar^b
Extract	Triterpene	Alkaloid	Anthraquinone	F	G	S	Flavonoid	Carotenoid	Tannin	Xanthone
Cassumunar ginger (Zingiber cassumunar)	−	+	−	−	−	−	++	−	−	−
Garlic (Allium Sativum)	−	+	−	−	−	−	−	−	−	−
Ginger (Zingiber officinale)	++	+++	−	−	−	−	+	+	−	−
Galangal (Alpinia galanga)	+	−	−	−	−	+	++	−	+	−
Indian long pepper (Piper chaba)	+	+	−	−	−	+	++	+	+	−
Pepper (Piper nigrum)	++	+	−	−	−	−	++	+	−	−
Myrobalan wood (Terminalia chebula)	−	++	−	−	−	++	+++	−	++	+++
Szechwan lovage rhizome (Ligusticum chuanxiong)	−	+++	−	−	−	+++	++	−	+	+
Golden shower (Cassia fistula)	+++	−	++	−	−	−	+++	−	+++	++
Myrtle grass (Acrous calamus)	−	++	−	−	−	−	++	−	−	−

^a+ = presence, − = absence.

^bF = fructose, G = glucose and S = sucrose.

Reagan-Shaw S, Nihal M, Ahmad N. (2008). Dose translation from animal to human studies revistied. FASEB 22:659–61

 PubMed Web of Science ®Google Scholar

Bhattacharya S, Ghosh AK. (2009). Phytosomes: The emerging technology for enhancement of bioavailability of botanicals and nutraceuticals. ISPUB 2. doi: 10.5580/1216

 Google Scholar

Manach C, Scalbert A, Morand C, et al. (2004). Polyphenols: Food sources and bioavailability. Am J Clin Nutr 79:727–47

 PubMed Web of Science ®Google Scholar